karya tulis akhir pengaruh kopi terhadap jumlah...
TRANSCRIPT
KARYA TULIS AKHIR
PENGARUH KOPI TERHADAP JUMLAH SEL MESANGIAL
GLOMERULUS GINJAL PADA TIKUS PUTIH STRAIN WISTAR
DIABETIK
Oleh :
EGA ASTARI
08020030
UNIVERSITAS MUHAMMADIYAH MALANG
FAKULTAS KEDOKTERAN
2011
HASIL PENELITIAN
PENGARUH KOPI TERHADAP JUMLAH SEL MESANGIAL
GLOMERULUS GINJAL PADA TIKUS PUTIH STRAIN WISTAR
DIABETIK
KARYA TULIS AKHIR
Diajukan kepada
Universitas Muhammadiyah Malang
untuk Memenuhi Salah Satu Persyaratan
dalam Menyelesaikan Program Sarjana
Fakultas Kedokteran
Oleh:
EGA ASTARI
08020030
UNIVERSITAS MUHAMMADIYAH MALANG
FAKULTAS KEDOKTERAN
2011
LEMBAR PENGESAHAAN
LAPORAN HASIL PENELITIAN
Telah disetujui sebagai hasil penelitian
untuk memenuhi persyaratan
Pendidikan Sarjana Fakultas Kedokteran
Universitas Muhammadiyah Malang
Tanggal : 17 Desember 2011
Pembimbing I
Prof. Dr. dr. Djoni Djunaedi Sp.PD KPTI.
Pembimbing II
dr. Ruby Riana Asparini Sp.BP.
Mengetahui,
Fakultas Kedokteran
Dekan,
dr. Irma Suswati, M.Kes.
LEMBAR PENGUJIAN
Karya Tulis Akhir oleh Ega Astari ini
telah diuji dan dipertahankan di depan Tim Penguji
Pada tanggal : 17 Desember 2011
Tim Penguji
Prof. Dr. dr. Djoni Djunaedi, Sp.PD KPTI. , Ketua
dr. Ruby Riana Asparini, Sp.BP. , Anggota
dr. Diah Hermayanti, Sp.PK. , Anggota
KATA PENGANTAR
Alhamdulillahirrabil’alamin, Puji syukur kehadirat Allah SWT yang telah
melimpahkan kurnianya sehingga penulis dapat menyelesaikan karya tulis akhir
yang berjudul “Pengaruh Kopi Terhadap Jumlah Sel Mesangial Glomerulus
Ginjal Pada Tikus Putih Strain Wistar Diabetik”. Penulisan penelitian ini
dilakukan dalam rangka memenuhi salah satu syarat untuk mencapai gelar
Sarjana Kedokteran Jurusan Pendidikan Dokter pada Fakultas Kedokteran
Universitas Muhammadiyah Malang.
Dalam menyelesaikan usulan penelitian ini, penulis banyak mendapatkan
bimbingan dan bantuan dari berbagai pihak. Oleh kerena itu dalam kesempatan
ini penulis mengucapkan terima kasih kepada :
1. dr. Irma Suswati, M.Kes, selaku Dekan Fakultas Kedokteran.
2. dr. Meddy Setiawan, Sp.PD, selaku Pembantu Dekan I Fakultas
Kedokteran.
3. dr. Fathiyah Safitri, M.Kes, selaku Pembantu Dekan II Fakultas
Kedokteran.
4. dr. Iwan Sis Indrawanto, Sp.KJ, selaku Pembantu Dekan III Fakultas
Kedokteran.
5. Prof. Dr. dr. Djoni Djunaedi, Sp.PD KPTI, selaku pembimbing I yang
telah meluangkan waktunya untuk membimbing dan mengoreksi demi
kesempurnaan penelitian ini.
6. dr. Ruby Riana Asparini, Sp.BP, selaku pembimbing II yang telah
meluangkan waktunya untuk memberi informasi dalam berbagai hal serta
memberi semangat dalam menyelesaikan penelitian ini.
7. dr. Diah Hermayanti, Sp.PK, selaku penguji yang telah memberi
tambahan ilmu dan kritik demi kesempurnaan penelitian ini.
8. dr. Soebarkah Basuki, Sp.PA, selaku pembaca hasil penelitian yang telah
memberikan ilmu dan bimbingan dalam pengamatan hasil penelitian.
9. Mas Aris Sandi beserta staf Lab. Kimia UMM, terima kasih banyak atas
segala bantuan, dukungan dan ilmu yang telah diberikan.
10. Mas Joko, mbak Tia, mbak Fat, mas Miftah, mbak Emi, mbak Dila dan
seluruh staf Lab. Terpadu FK UMM, terima kasih banyak atas bantuan
dan dukungannya.
11. Seluruh staf Tata Usaha FK UMM (Pak Yono, Bu Rom, Mas Didit, dan
Mas Faisal). Terima kasih atas bantuannya selama ini.
12. Orang tua dan keluarga saya di Jakarta yang telah memberikan bantuan
dukungan material dan moral.
13. Vivin Novia Rini dan Alifaneta Yustisiani yang telah menjadi teman
diskusi yang baik dan memberi banyak masukan serta dukungan dalam
menyelesaikan penelitian ini.
14. Sahabat yang telah banyak membantu dan memberikan semangat dalam
menyelesaikan penelitian ini.
15. Teman-teman angkatan 2008 Fakultas Kedokteran UMM, terima kasih
atas dukungan dan do’a sehingga dapat menyelesaikan tugas akhir ini.
Penulis menyadari bahwa penelitian ini masih belum sempurna, untuk itu
kritik dan saran kami harapkan demi kesempurnaan, serta kami mengharapkan
agar usulan penelitian ini dapat berguna bagi kita semua, serta bermanfaat untuk
bidang kedokteran.
Malang, Desember 2011
Penulis
ABSTRAK
Astari, Ega. 2011. Pengaruh Kopi Terhadap Jumlah Sel Mesangial Glomerulus
Ginjal Pada Tikus Putih Strain Wistar Diabetik. Tugas Akhir, Fakultas
Kedokteran, Universitas Muhammadiyah Malang. Pembimbing: (1) Djoni
Djunaedi (2) Ruby Riana Asparini
Pendahuluan : Kopi merupakan salah satu minuman kegemaran masyarakat
dunia. Berbagai penelitian membuktikan bahwa kopi dapat menurunkan risiko
DM tipe II. Penelitian mengenai kopi sebagai terapi alternatif dan preventif
terhadap komplikasi kronik DM dengan melihat jumlah sel mesangial glomerulus
ginjal belum pernah dilakukan di Indonesia.
Tujuan : Membuktikan pengaruh kopi terhadap jumlah sel mesangial glomerulus
ginjal pada tikus putih strain wistar diabetik.
Metode : Eksperimen laboratoris rancangan the post test only control group
desain. Sampel tikus putih strain wistar dibagi 4 kelompok. Sampel I : kontrol
negatif, II: kontrol positif, dua kelompok lainnya diberikan kopi Robusta berbagai
dosis (5,4 mL/200 gr BB/ hari, 10,8 mL/200 gr BB/hari). Analisis data
menggunakan One Way Anova, uji Tukey 1%, uji korelasi dan uji regresi linier.
Hasil : Hasil uji One Way Anova menyatakan nilai sig (2-tailed) = 0,000 < p
(0,01) artinya terdapat pengaruh perlakuan dengan perbedaan yang bermakna
terhadap jumlah sel mesangial. Dari hasil uji Tukey1%, didapatkan notasi yang
berbeda dari tiap-tiap kelompok yang artinya berbeda nyata. Uji korelasi
menghasilkan nilai sig (2-tailed) = 0,000 < p (0,01) artinya terdapat korelasi yang
berbanding terbalik dan sangat kuat antara dosis kopi dan jumlah sel mesangial
glomerulus ginjal tikus putih diabetik dengan nilai Pearson Correlation -0,969,
sedangkan hasil uji regresi didapatkan nilai R2 = 0,939 artinya hampir semua
jumlah sel mesangial dapat dipengaruhi oleh kenaikan dosis kopi Robusta.
Kesimpulan : Pemberian kopi berbagai dosis dapat menurunkan jumah sel
mesangial glomerulus ginjal tikus diabetik.
Kata kunci : DM tipe II, jumlah sel mesangial, kopi Robusta
ABSTRACT
Astari, Ega. 2011. The Influence of Coffee toward The Number of Renal’s
Glomerular Mesangial Cells in Diabetic Wistar Strain White Mice
Models. Final Assignment, Medical Faculty, University of
Muhammadiyah Malang, Adviser: (1) Djoni Djunaedi (2) Ruby Riana
Asparini
Introduction : Coffee is one of several favorite drink in the world. Various
experiments prove that coffee can reduce the risk of diabetes type II. Study about
coffee as the alternative and preventive therapies in diabetic chronic
complications by observing the number of glomerular mesangial cell is not yet
been conducted in Indonesia.
Objective : Understanding the effect of coffee toward the number of renal’s
glomerular mesangial cells in diabetic wistar strain white mice models.
Method : Laboratory experiment the post test only control group design. Wistar
white mice groups were divided into 4 groups. Sample I : negative control, II:
positive control, the other two groups were treated with Robusta coffee in various
doses (5,4 mL/200 grBW/day, 10,8 mL/200 gr BW/day). Data analysis used One
Way Anova, Tukey test 1%, correlation test, and linear regression test.
Result : One way Anova test result’s revealed of value sig (2-tailed) = 0,000 < p
(0,01) which meant that there were an influence of treatments with the obviously
different toward the number of mesangial cells. From Tukey test 1% result, it was
obtained different notation from each groups which meant obviously different.
The correlation test result of value (2-tailed) = 0,000 < p (0,01) which meant there
were an obviously and strongly correlation between coffee doses and the number
of renal’s glomerular mesangial cells in diabetic white mice models with the
value of Pearson Correlation -0,969, while regression test result was R2 = 0,939
which meant that almost of all mesangial cells number can influenced by
increasing doses Robusta coffee.
Conclusion : Coffee administration in various doses can reduce the number of
renal’s glomerular mesangial cells in diabetic mice models.
Keywords : diabetes type II, the number of mesangial cells, Robusta coffee
DAFTAR ISI
Halaman
HALAMAN JUDUL ......................................................................................... i
LEMBAR PENGESAHAN ............................................................................... iii
LEMBAR PENGUJIAN .................................................................................... iv
KATA PENGANTAR ...................................................................................... v
ABSTRAK ........................................................................................................ vii
ABSTRACT ...................................................................................................... viii
DAFTAR ISI ..................................................................................................... ix
DAFTAR TABEL ............................................................................................. xiv
DAFTAR GAMBAR ........................................................................................ xv
DAFTAR SINGKATAN .................................................................................. xvii
DAFTAR LAMPIRAN ..................................................................................... xx
BAB 1 PENDAHULUAN ................................................................................ 1
1.1 Latar Belakang .................................................................................. 1
1.2 Rumusan Masalah ............................................................................. 3
1.3 Tujuan ............................................................................................... 4
1.3.1 Tujuan umum ………………………………………....……..4
1.3.2 Tujuan khusus ........................................................................ 4
1.4 Manfaat Penelitian ............................................................................ 4
1.4.1 Manfaat akademis .................................................................. 4
1.4.2 Manfaat klinis ........................................................................ 4
1.4.3 Manfaat masyarakat ............................................................... 4
1.5 Keterbatasan Penelitian ..................................................................... 5
BAB 2 TINJAUAN PUSTAKA ....................................................................... 6
2.1 Kopi .................................................................................................. 6
2.1.1 Taksonomi ...............................................................................6
2.1.2 Sejarah Kopi ........................................................................... 7
2.1.3 Kopi Robusta .......................................................................... 8
2.1.4 Pembuatan minuman kopi ...................................................... 8
2.1.5 Manfaat kopi ........................................................................... 10
2.1.6 Kandungan Kopi Robusta ....................................................... 11
2.1.6.1 Kafein ........................................................................ 11
a. Definisi dan struktur kimia kafein ........................ 11
b. Kadar kafein dalam kopi ...................................... 13
c. Dosis rekomendasi kafein ..................................... 14
d. Absorpsi, distribusi, dan metabolisme kafein ....... 14
e. Efek kafein bagi kesehatan ................................... 15
2.1.6.2 Chlorogenic acid ..................................................... 16
2.2 Diabetes Mellitus .............................................................................. 20
2.2.1 Definisi dan klasifikasi klinis ................................................ 20
2.2.2 Diagnosis .............................................................................. 22
2.3 Nefropati Diabetik .............................................................................. 22
2.4 Struktur Ginjal ................................................................................... 25
2.4.1 Anatomi ginjal ........................................................................ 25
2.4.2 Histologis ginjal ...................................................................... 26
2.5 Komplikasi Kronik Diabetes Mellitus .............................................. 32
2.5.1 Advanced Glycation End Products (AGEs) ............................ 33
2.5.2 Jalur Poliol – Sorbitol (Aldose Reduktase) .............................. 34
2.5.3 Protein Kinase C (PKC) ........................................................... 36
2.5.4 Jalur Hexosamine ..................................................................... 37
2.6 Bahan penginduksi terjadinya Diabetes Mellitus .............................. 38
2.7 Nicotinamide ………………………………………………………...42
2.8 Mekanisme Kerja Kopi Terhadap Kerusakan Glomerulus
Ginjal ................................................................................................... 44
BAB 3 KERANGKA KONSEP DAN HIPOTESIS ......................................... 46
3.1 Kerangka Konsep ............................................................................. 46
3.2 Hipotesis ........................................................................................... 49
BAB 4 METODE PENELITIAN ...................................................................... 50
4.1 Rancangan Penelitian ....................................................................... 50
4.2 Lokasi ............................................................................................... 50
4.3 Populasi dan Sampel ......................................................................... 50
4.3.1 Populasi .................................................................................. 50
4.3.2 Sampel ..................................................................................... 50
4.3.3 Replikasi ................................................................................. 50
4.3.4 Karakteristik sampel penelitian .............................................. 52
4.4 Variabel Penelitian dan Definisi Operasional .................................. 52
4.4.1 Variabel bebas ........................................................................ 52
4.4.2 Variabel tergantung ................................................................ 52
4.4.3 Variabel kontrol ...................................................................... 52
4.4.4 Definisi operasional ................................................................ 52
4.5 Alat dan Bahan .................................................................................. 54
4.5.1 Alat ......................................................................................... 54
4.5.2 Bahan ...................................................................................... 55
4.6 Prosedur Penelitian ........................................................................... 56
4.6.1 Adaptasi hewan percobaan ..................................................... 56
4.6.2 Penentuan dosis ...................................................................... 56
4.6.3 Penyiapan larutan uji .............................................................. 57
4.6.4 Pengambilan darah tikus ......................................................... 58
4.6.5 Percobaan ................................................................................ 58
4.7 Analisis Data ..................................................................................... 63
4.8 Alur Penelitian .................................................................................. 64
BAB 5 HASIL PENELITIAN DAN ANALISIS DATA ................................. 65
5.1 Hasil Penelitian ................................................................................. 65
5.1.1 Hasil Pengukuran Glukosa Darah dengan Metode
GOD-PAP ............................................................................... 65
5.1.2 Hasil Pengamatan Preparat Glomerulus Ginjal Tikus ............ 68
5.1.3 Jumlah sel mesangial tiap kelompok ...................................... 69
5.2 Analisis Data ...................................................................................... 71
5.2.1 Uji Anova ............................................................................... 71
5.2.2 Uji Tukey1% .......................................................................... 72
5.2.3 Uji Korelasi ............................................................................ 73
5.2.4 Uji Regresi .............................................................................. 73
BAB 6 PEMBAHASAN ................................................................................... 75
BAB 7 KESIMPULAN DAN SARAN ............................................................ 82
DAFTAR PUSTAKA ....................................................................................... 83
LAMPIRAN ...................................................................................................... 91
DAFTAR TABEL
Tabel Halaman
5.1 Rerata glukosa darah setelah injeksi nicotinamide dan
Streptozotocin ............................................................................................. 66
5.2 Rerata glukosa darah pada hari ke-43 ......................................................... 67
5.3 Jumlah sel mesangial glomerulus ginjal ..................................................... 70
5.4 Uji Anova jumlah sel mesangial glomerulus ginjal .................................... 72
5.5 Rekap Uji Tukey1% jumlah sel mesangial ................................................. 73
DAFTAR GAMBAR
Gambar Halaman
2.1 Bunga Kopi ............................................................................................... 6
2.2 Buah Kopi Robusta ................................................................................... 7
2.3 Biji Kopi Robusta ...................................................................................... 7
2.4 Komposisi Kimia Biji Kopi Robusta yang disangrai ................................ 11
2.5 Struktur Kimia Kafein ............................................................................... 12
2.6 Beberapa kelas utama senyawa phenolic .................................................. 17
2.7 Struktur Kimia Chlorogenic acid .............................................................. 18
2.8 Klasifikasi Etiologi Diabetes Mellitus ...................................................... 21
2.9 Biopsi ginjal pasien DM tipe 2 dengan ekspansi mesangial ..................... 24
2.10 Struktur Umum Histologis Ginjal ............................................................. 27
2.11 Struktur Nefron Ginjal .............................................................................. 28
2.12 Glomerulus ginjal normal ......................................................................... 30
2.13 Mekanisme molekular komplikasi yang berhubungan dengan diabetes ... 32
2.14 Pembentukan peningkatan produk akhir glikasi lanjut (AG) .................... 33
2.15 Jalur Poliol – Sorbitol ............................................................................... 34
2.16 Jalur PKC (Protein Kinase C) ................................................................... 36
2.17 Peningkatan Kegiatan Hexosamine Pathway ............................................ 37
2.18 Struktur kimia streptozotocin .................................................................... 39
2.19 Gambar skema mekanisme STZ ............................................................... 41
2.20 Struktur kimia Nicotinamide ..................................................................... 42
4.1 Konversi dosis antar spesies ...................................................................... 57
5.1 Diagram batang rerata hasil pengukuran kadar glukosa darah 2 jam PP dan
kadar glukosa darah puasa setelah injeksi nicotinamide & streptozotocin
pada hari ke-15 ........................................................................................ 66
5.2 Diagram batang rerata hasil pengukuran kadar glukosa darah 2 jam PP dan
kadar glukosa darah puasa pada hari ke-43 ............................................. 67
5.3 Gambaran histologis glomerulus ginjal tikus ........................................... 69
5.4 Diagram rerata hasil perhitungan jumlah sel mesangial pada tiap – tiap
kelompok perlakuan ................................................................................. 70
5.5 Grafik uji regresi antara dosis kopi dengan jumlah sel mesangial glomerulus
ginjal ....................................................................................................... 74
DAFTAR SINGKATAN
ADP : Adenosine Diphosphate
AGEs : Advanced Glycation End Products
AMP : Adenosine Monophosphate
AR : Aldose Reduktase
ATP : Adenosine Triphosphate
cAMP : cyclic Adenosine Monophosphate
CGA : Chlorogenic acid
DAG : Diasilgliserol
DM : Diabetes Melitus
DNA : Deoxyribose Nucleic Acid
Dpl : di bawah permukaan laut
eNOS : endothelial Nitric Oxide Synthase
GABA : Gamma-Aminobutyric Acid
GFAT : Glutamin Fruktosa-6-Fosfat Amidotransferase
GI : Gastro Intestinal
GLUT : Glucose Transporter
GMP : Guanosine Monophosphate
ICAM-1 : Inter Cellular Adhesion Molecule-1
IDDM : Insulin Dependent Diabetes Mellitus
IL : Interleukin
LD : Lethal Dose
LDL : Low Density Protein
MAPK : Mitogen Activated Protein Kinase
MCP-1 : Monocyte Chemoattractant Protein-1
MCR : Metabolic Clearance Rate
NAD : Nicotinamide Adenine Dinucleotide
NADH : Nicotinamide Adenine Dinucleotide Hydrogenase
NADP : Nicotinamide Adenine Dinucleotide Phosphate
NADPH :Nicotinamide Adenine Dinucleotide Phosphate
Hydrogenase
NF-қB : Nuclear Factor Kappa B
NO : Nitric Oxide
NOD : Non-Obese Diabetes
PAI-1 : Plasminogen Activator Inhibitor 1
PBS : Phosphate Buffered Saline
PKC : Protein Kinase C
PP : Post Prandial
RAGE : Receptor for Advanced Glycation End Product
RNA : Ribo Nucleic Acid
ROS : Reactive Oxygen Species
SDH : Sorbitol Dehydrogenase
SHBG : Sex Hormone Binding Globulin
STZ : Streptozotocin
TGF-β : Transforming Growth Factor β
TNF-α : Tumor Necrotizing Factor α
VCAM-1 : Vascular Cell Adhesion Molecule-1
VEGF : Vascular Endothelial Growth Factor
γ-GT : Gamma-Glutamyl Transpeptidase
DAFTAR LAMPIRAN
Lampiran
1. Data Pengamatan Glukosa Darah dan jumlah sel mesangial ....................... 90
2. Analisis Data Kadar Glukosa Darah ............................................................. 94
3. Analisis Data Jumlah Sel Mesangial ............................................................. 105
DAFTAR PUSTAKA
American Association of Clinical Endocrinologists, 2007, Medical Giudelines for
Clinical Practice for The Management of Diabetes Mellitus, Endocrine
Practice 13 (Suppl 1)
American Diabetes Association, 2009, Diagnosis and Classification of Diabetes
Mellitus, Diabetes Care 32 (S): 62-7
American Diabetes Association, 2009, Definition and Description of Diabetes
Mellitus, Diabetes Care 32 (S): 62
Andersen L, 2006, Consumption of coffee is associated with reduced risk of death
attributed to inflammatory and cardiovascular diseases in the lowa
Women’s Health Study, Am J Clin Nutr, 83(5): 1039-46
Andersen P, 2002, Handbook of Clinical Drug Data 10th
Edition, International
edition, University of California
Anonim, 2008, VILDAGLIPTIN 50 mg: Terapi Baru Diabetes Melitus
Tipe2.http://www.dexamedica.com/newsandmedia/news/detail.php?idc=1
&id=3 68 (2 Maret 2010)
Aronson, Doron, 2005, Atherothrombosis and Coronary Artery Disease,
Diabetes, Obesity, and The Metabolic Syndrome, 2nd
edition,
Philadelphia: Lippincott Williams & Wilkins
Barik R, Jain S, Qwarta D, et al, 2008, Antidiabetic Activity of Aqueous Root
Extract of Ichnocarpus frutecens in STZ-Nicotinamide Induced Type II
Diabetic in Rats, Research article India
Bidaya E, Tjokroprawiro A, 1987, Nefropati Diabetik, Cermin Dunia Kedokteran 43
Biesenbach G, Janko O, Zasgornick J, et al, 1994, Similiar rate of progression in
thepredialysis phase in type I and type II diabetes mellitus, Nephrol Dial
Transplant, 9: 1097-102
Brown A, 2008, Understanding Food: Principles and Preparation, AS :
Thomson Learning, pp: 518-521
Brownlee M, Aiello L. P, Cooper ME, et al, 2008, Complications of Diabetes
Mellitus, in: Meloni D, Snyder A, Williams Textbook of Endocrinology,
11th
ed. Philadelphia: Saunders Elsevier, 1422-1448
Castillo MD, Ames JM, Gordon MH, et al, 2002, Effect of roasting on the
antioxidant activity of coffee brews, J Agric Food Chem, 19;50 (13);
3698-703
Chandrasoma P, Clive RT, 2005, Ringkasan Patologi Anatomi, Edisi II, Jakarta:
EGC, pp: 629-30
Choi HK, Willet W, Curhan G, et al, 2007, Coffee consumption and risk of
incident gout in men : A prospective study, Arthr Rheum, 56(6): 2049-55
Clarke RJ, Macrae R, (Editors), 1985, Coffee Vol. 1 : Chemistry, London :
Elsevier Applied Science Publishers, pp: 306
Clifford MN, 2003, The analysis and characterization of chlorogenic acids and
other cinnamates, In : Santos-Buelga G, Williamson G, editors, In :
Methods in Polyphenol Analysis, Cambridge : Royal Society of Chemistry,
314-337
Cotran RS, Rennke H, Kumar V, et al, 2007, Ginjal dan Sistem Penyalurnya,
Dalam: Kumar V, Cotran RS, Robbins SL, (eds), Buku Ajar Patologi
Robbins Volume 2, Edisi VII, Jakarta: EGC, pp: 572, 594-7
Daglia M, Papetti A, Gregotti C, et al, 2000, In vitro antioxidant and ex vivo
protective activities of green and roasted coffee, J Agric Food Chem, 48
(5), 1449-54
Daglia M, Racchi M, Papetti A, et al, 2004, In vitro and ex vivo antihydroxyl
radical activity of green and roasted coffee, J Agric Food Chem, 52 (6):
1700-4
Davey P, 2006, At a Glance Medicine, Jakarta: Erlangga, p: 57
Djatmika F, 2007, Pengaruh Infusa Herba Meniran (Phyllantus niruri Linn)
Terhadap Penurunan Kadar Asam Urat Serum Darah Tikus Putih Jantan
Galuh Wistar Hiperurisemia
Donatus IA, Suhardjono D, Nurlaila, et al, 1992, Petunjuk Praktikum Toksikologi
Edisi 1, Yogyakarta : Laboratorium Farmakologi dan Toksikologi,
Fakultas Farmasi, Universitas Gajah Mada, Yogyakarta
Dorland, 2002, Kamus Kedokteran, EGC, Jakarta
Duff RL, 2006, American Dietetic Association Complete Food and Nutrition
Guide, Kanada : John Wiley & Sons, Inc, pp: 167-169
Effendi I, Markum H, 2007, Pemeriksaan Penunjang pada Penyakit Ginjal, Dalam
: Sudoyo A, Setiyahada B, Alwi I, Simadibrata M, Setiati S, (eds), Buku
Ajar Ilmu Penyakit Dalam Jilid I, Edisi IV, Jakarta : Pusat Penerbitan
Departemen Ilmu Penyakit Dalam FKUI, pp: 505-9
Firdous MR, Koneri CH, Sarvaradu, et al, 2009, NIDDM Antidiabetic Activity of
saponins of Momordica cymbalaria in Streptozotocin-Nicotinamide
Departement of Pharmacology, RR College of Pharmacy, Bangalore,
India, (3). P.. 1460-1465
Fitrantia, JB, 2011, Komplikasi kardiovaskular dan ginjal pada diabetes, (online)
diakses 8 November 2011, <www.medicinesia.com>
Focosi D, 2009, Physiology of Adult Homo Sapiens-Urinary Apparatus,
http://www6.ufrgs.br/favet/imunovet/molecular_immunology/kidney.html.
(27 Februari 2010)
Foster DW, 2000, Diabetes Mellitus. Prinsip-Prinsip Ilmu Penyakit Dalam
Horrison, Jakarta : EGC, pp: 2196-2217
Fredholm BB, Battg K, Holmen J, et al, 1999, Actions of Caffeine in Brain with
Special Reference to Factors That Contribute to Its Widespread Use,
Pharmacol Rev. 51 (1) : 83-133
Gartner JP, Hiatt JL, 2007, Color Text Book of Histology, 3th ed, Philadelphia :
Elsevier Saunders, pp: 437-45
Glassock RJ, 1990, Focus on Proteinuria, J Am Soc Nephrol, 10:88-93
Guyton and Hall, 2007, Buku Ajar Fisiologi Kedokteran, Edisi : 9, Jakarta: EGC, pp:
1221-37
Ha H, Lee HB, 2003, Reactive Oxygen Species and Matrix Remodeling in
Diabetic Kidney, J Am Soc Nephrol, 14: S246–S249
Hendromartono, 2007, Buku Ajar Ilmu Penyakit Dalam, Jakarta : Pusat Penerbitan
Departemen Ilmu Penyakit Dalam FK-UI, pp: 1900
James JE, Caffeine and Health, 1984, IN : Spiller GA, Liss AR, editors, Progress
in Clinical and Biological Research. Volume 158, New York: Academic
Press
Jassim SAA, Naji MA, 2003, Novel antiviral agents: a medicinal plant
perspective, J Appl Microbiol, 95 (3): 412-27
Johnston KL, Clifford MN, Morgan LM, 2003, Coffee acutely modifies
gastrointestinal hormone secretion and glucose tolerance in humans:
glycemic effects of chlorogenic acid and caffeine, Am J Clin Nutr, 79 (4):
728-33
Junqueira LE, Carneiro J, Kelley RO, et al, 2005, Basic Histology, 11th ed,
Boston: Mc Graw-Hill, pp : 373-90
Katzung BG, 2002, Farmakologi: Dasar dan Klinik Buku 2, Edisi I, Jakarta:
Salemba Medika, pp: 484-6
Knip M, Douek IF, Moore WP, et al, 2000, Safety of high-dose nicotinamide: a
review, Diabetologia, 43 (11): 1337–45
Lachane MP, 2006, The Pharmacology and Toxicology of Caffeine, J Food
Savety, 71-112.
Lawrence P, Reagan, 2000, Neuronal Vulnerability in Diabetes: Changes in
Neuronal Structure Related to Glycemic States - Workshop on
Hypoglycemia and the Brain, http://www.jdrf.org ( 1 November 2008)
Lenzen S, 2008, Review: The mechanisms of alloxan-and streptozotocin-induced
Diabetes, Diabetologia, 51: 216–226
Liu S, et al, 2009, Sex Hormone-Binding Globulin and Risk of Type 2 Diabetes
in Women and Men, The New England Journal of Medicine, 361:1152-63
Marks DB, Marks AD, Smith CM, 2000, Biokimia Kedokteran Dasar Ed ke-1,
Penterjemah : Pendit BU, Jakarta: EGC, p: 523-24
Marsh T, 2006, Review of the Aceh Coffee Industry, UNDP ERTR Livelihood
Component, P: 9
Morton, Lincoln W, Rima ACC, et al, 2007, Chemistry And Biological Effects of
Dietary Phenolic Compounds: Relevance To Cardiovascular Disease, Clin
Exp Pharmacol and Physiol, 27(3): 152-59
Muljana W, 2006, Bercocok Tanam Kopi, Semarang: CV Aneka Ilmu, p: 12
Mycek MJ, Harvey RA, Champe PC, 1995, Stimulan Susunan Saraf Pusat.
Farmakologi Ulasan Bergambar, Edisi ke-2, Jakarta: Widya Medika
Najiyati S, Danarti, 2007, Kopi Budi Daya dan Penanganan Pascapanen, Jakarta:
Penebar Swadaya, pp:18-20
Nardini M, Cirillo E, Natella F, et al, 2002, Detection of bound phenolic acids:
Prevention by ascorbic acid and ethylenediaminetetraacetic acid of
degradation of phenolic acids during alkaline hydrolysis, Food Chem, 79:
119-24
Natella F, Nardini M, Giannetti E, et al, 2002, Coffee drinking increases plasma
antioxidant capacity in humans, J. Agric. Food Chem, 50: 6211-216
Odegaard AO, Pereira MA, Koh W, et al, 2008, Coffee, tea, and incident type 2
diabetes: the Singapore Chinese health study, Am J Clin Nutr, 88: 979-85
Passero K, 2011, NADH Supplements and Information, (online) diakses 30
Januari 2011, <www.nutrasanus.com>
Paulsen DF, 2000, Histology and Cell Biology: Examination and Board Review,
4th ed. Singapura: Mc Graw-Hill Book Co, pp: 244-6
Pellegrini N, 2003, Total antioxidant capacity of plant foods, beverages and oils
consumed in Italy assessed by three different in vitro assays, Journal of
Nutrition, 33: 2812-2819
Pimentel D, Zemdegsi CS, Theodoro A, et al, 2009, Diabetology & Metabolic
Syndrome : Does long-term coffee intake reduce type 2 diabetes mellitus
risk?, BioMed Central, pp: 1-8
Powers AC, 2005, Diabetes Mellitus, in: Kasper DL, et al. Harrison’s Principles
of Internal Medicine, 16th
edn. USA: McGraw-Hill, pp. 2154-2155
Price & Wilson, 2006, Pankreas : Metabolisme Glukosa dan Diabetes Mellitus,
Patofisiologi : Konsep Klinis Proses – Proses Penyakit, Jakarta: EGC,
1268-1270
Rees DA, Alcolado JC, 2005, Animal models od diabetes mellitus, Diabetic
Medicine, 22 : 359-370
Richelle M, Tavazzi I, Offord E, et al, 2001, Comparison of the antioxidant
activity of commonly consumed polyphenolic beverages (coffee, cocoa,
and tea) prepared per cup serving, Journal of Agriculture Food
Chemistry, 49(7): 23438-703
Richelle M, Tavazzi I, Offord E, et al, 2001, Comparison of the antioxidant
activity of commonly consumed polyphenolic beverages (coffee, cocoa,
and tea) prepared per cup servin, Journal of Agriculture Food Chemistry,
49(7): 3438-3442
Robert C, Sandier S, Hellerstrem, 1984, Multiple Low-Dose Streptozotocin-
Induced Diabetes in Mouse, Departement of Anatomy Pediatrics, Mount
Sinai School of Medicine of the City University of New York, NewYork
Roesli R, 1996, Study on the prevalence of non-insulin dependent diabetes and
impaired glucose tolerance in rural area of West Java, Indonesia,
Highlighting
Rohdiana, Dadan, 2009, Teh Ini Menyehatkan, Bandung: Alfabeta
Ross AJ, Kasum MC, 1994, Dietary flavonoids and risk coronary heart disease,
Nutr Rev, 52: 59-61
Ruskar AGN, 2010, Kajian Efektivitas Streptozotocin Dalam Induksi Tikus Putih
Diabetik, Surabaya, Departemen Biologi, Fakultas Sains dan Teknologi,
Universitas Airlangga, Skripsi
Salazar ME, Willet A, Ascherio, et al, 2003, Coffee consumption and risk of type
2 diabetes in men and women, Diabetes, 52: A72
Schnedl WJ, Ferber S, Johnson JH, et al, 1994, STZ transport and
Cytotoxicity, Specific enhancement in GLUT2-expressing cells, Diabetes
43(11): 1326–33
Setiawan B, Suhartono E, 2005, Stres oksidatif dan peran antioksidan pada diabetes
melitus, Majalah Kedokteran Indonesia 55 (2):87
Shafrir E, 2007, Animal Models of Diabetes, Taylor dan Francis Group, United
States
Silbernagl & Lang, 2007, Teks dan Atlas Berwarna Patofisiologi, Jakarta: EGC
Soehardjono J, 1990, Petunjuk Laboraturium : Percobaan Hewan Laboraturium,
Yogyakarta, p: 197-217
Soman, 2009, Diabetic Nephopathy, http://emedicine.medscape.com (31 Oktober
2010)
Sotillo RD, Hadey M, 2007, Nonmutagenic Antioxidant with Potential
Antimicrobial Activity, J Food Sci, 63 (5): 907
Stevens A, Lowe JS, 2005, Human Histology, 3th ed, Philadelphia: Elsevier
Saunders, pp: 300-294
Sudarmoko A, 2010, Tetap Tersenyum Melawan Diabetes, Yogyakarta : Atma
Jaya Press, p: 40
Svilaas A, Sakhi A, Andersen L, et al, 2004, Intakes of antioxidants in coffee,
wine, and vegetables are correlated with plasma caretenoids in humans, J
Nutr, 134: 562-7
Szkudelski T, 2001, The mechanism of alloxan and streptozotocin action in b
cells of the rat pancreas, Physiol Res, 50(6):537-46
Tjekyan RM, 2007, Risiko Penyakit Diabetes Mellitus Tipe 2 di Kalangan
Peminum Kopi di Kotamadya Palembang Tahun 2006-2007, Makara,
Kesehatan, Volume 11, No. 2: 54-60
Tukiran FB, 2009, Efek Ekstrak Etanolik Poliherbal “MERTOPACING” Terhadap
Gambaran Histologik Ginjal Pada Tikus Diabetik Yang Diinduksi
Streptozotocin, Yogyakarta: Fakultas Kedokteran Universitas Gadjah Mada
Tormo MA, Gil-Exojo L, Romero A, et al, 2006, White bean amylase inhibitor
administered orally reduces glycaemia in type 2 diabetic rats, British
Journal of Nutrition, 96(3): 539-544
Van Dam RM, Feskens, 2002, Coffee consumption and risk of type 2 diabetes
mellitus, Lancet, 360: 1477-1478
Waspadji, Sarwono, 2007, Komplikasi Kronik Diabetes: Mekanisme Terjadinya,
Diagnosis, dan Strategi Pengelolaan. Dalam: Buku Ajar Ilmu Penyakit
Dalam. Edisi IV. Jakarta: Fakultas Kedokteran Universitas Indonesia,
1886-1888
Wang Z, Gleichmann H, 1998, GLUT2 in pancreatic islets: crucial target moleculein
diabetes induced with multiple low doses of streptozotocin in mice, Diabetes,
47 (1): 50–6.
Winarsi H, 2009. Antioksidan Alami & Radikal Bebas, Yogyakarta: Kanisius, pp:
204-211
Yulianti T, 2010, Informasi Laboratorium No. 1/2010: Sex Hormone Binding
Globulin.http://prodia.meta-
technology.net/ilmiah_detail.php?id=91&pagenum=1&lang=ina (25 April
2011)
Yusianto, 1999, Kopi : Pengolahan Mutu, Komposisi Kimia, Citarasa. Jember: Pusat
Penelitian Kopi dan Kakao
Zhang, Sarah X, Joshua J, et al. 2006. Therapeutic Potential of Angiostatin in
Diabetic Nephropathy, J Am Soc Nephrol, 17: 475-486