A model of type 2 diabetes in the guinea pig using sequential diet-induced glucose intolerance and streptozotocin treatment

被引:53
作者
Podell, Brendan K. [1 ]
Ackart, David F. [1 ]
Richardson, Michael A. [1 ]
DiLisio, James E. [1 ]
Pulford, Bruce [1 ]
Basaraba, Randall J. [1 ]
机构
[1] Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA
基金
美国国家卫生研究院;
关键词
Animal model; Insulin-independent diabetes; Guinea pig; Glucose intolerance; Streptozotocin; Type; 2; diabetes; BETA-CELL MASS; ANIMAL-MODELS; INFECTIOUS-DISEASES; DIABETOGENIC ACTION; MICE; MELLITUS; RAT; ATHEROSCLEROSIS; INFLAMMATION; NEPHROPATHY;
D O I
10.1242/dmm.025593
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Type 2 diabetes is a leading cause of morbidity and mortality among noncommunicable diseases, and additional animal models that more closely replicate the pathogenesis of human type 2 diabetes are needed. The goal of this study was to develop a model of type 2 diabetes in guinea pigs, in which diet-induced glucose intolerance precedes beta-cell cytotoxicity, two processes that are crucial to the development of human type 2 diabetes. Guinea pigs developed impaired glucose tolerance after 8 weeks of feeding on a high-fat, high-carbohydrate diet, as determined by oral glucose challenge. Diet-induced glucose intolerance was accompanied by beta-cell hyperplasia, compensatory hyperinsulinemia, and dyslipidemia with hepatocellular steatosis. Streptozotocin (STZ) treatment alone was ineffective at inducing diabetic hyperglycemia in guinea pigs, which failed to develop sustained glucose intolerance or fasting hyperglycemia and returned to euglycemia within 21 days after treatment. However, when high-fat, high-carbohydrate diet-fed guinea pigs were treated with STZ, glucose intolerance and fasting hyperglycemia persisted beyond 21 days post-STZ treatment. Guinea pigs with diet-induced glucose intolerance subsequently treated with STZ demonstrated an insulin-secretory capacity consistent with insulin-independent diabetes. This insulin-independent state was confirmed by response to oral antihyperglycemic drugs, metformin and glipizide, which resolved glucose intolerance and extended survival compared with guinea pigs with uncontrolled diabetes. In this study, we have developed a model of sequential glucose intolerance and beta-cell loss, through high-fat, high-carbohydrate diet and extensive optimization of STZ treatment in the guinea pig, which closely resembles human type 2 diabetes. This model will prove useful in the study of insulin-independent diabetes pathogenesis with or without comorbidities, where the guinea pig serves as a relevant model species.
引用
收藏
页码:151 / 162
页数:12
相关论文
共 71 条
[1]  
[Anonymous], 2015, DIABETES ATLAS
[2]   THE MAKING OF DIABETIC GUINEA-PIGS BY STREPTOZOTOCIN AND HIGH-INCIDENCE OF TRIGGERED ACTIVITY IN THE VENTRICULAR MUSCLE [J].
AOMINE, M ;
NOBE, S ;
ARITA, M .
JAPANESE JOURNAL OF PHYSIOLOGY, 1990, 40 (05) :651-663
[3]   EFFECTS OF YOHIMBINE AND NICOTINIC-ACID ON INSULIN-SECRETION IN ISLET TRANSPLANTED STREPTOZOTOCIN-DIABETIC RATS [J].
ARRAJAB, A ;
AHREN, B .
DIABETES RESEARCH AND CLINICAL PRACTICE, 1991, 11 (02) :81-87
[4]   Increased Small Dense LDL and Decreased Paraoxonase Enzyme Activity Reveals Formation of an Atherogenic Risk in Streptozotocin-Induced Diabetic Guinea Pigs [J].
Aslan, Mutay ;
Ozcan, Filiz ;
Kucuksayan, Ertan .
JOURNAL OF DIABETES RESEARCH, 2013, 2013
[5]   Global estimates of undiagnosed diabetes in adults [J].
Beagley, Jessica ;
Guariguata, Leonor ;
Weil, Clara ;
Motala, Ayesha A. .
DIABETES RESEARCH AND CLINICAL PRACTICE, 2014, 103 (02) :150-160
[6]   MOLECULAR-BIOLOGY OF MAMMALIAN GLUCOSE TRANSPORTERS [J].
BELL, GI ;
KAYANO, T ;
BUSE, JB ;
BURANT, CF ;
TAKEDA, J ;
LIN, D ;
FUKUMOTO, H ;
SEINO, S .
DIABETES CARE, 1990, 13 (03) :198-208
[7]   ANIMAL-MODELS OF DIABETES-MELLITUS - PHYSIOLOGY AND PATHOLOGY [J].
BELL, RH ;
HYE, RJ .
JOURNAL OF SURGICAL RESEARCH, 1983, 35 (05) :433-460
[8]   Development of a novel polygenic model of NIDDM in mice heterozygous for IR and IRS-1 null alleles [J].
Bruning, JC ;
Winnay, J ;
BonnerWeir, S ;
Taylor, SI ;
Accili, D ;
Kahn, CR .
CELL, 1997, 88 (04) :561-572
[9]   β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes [J].
Butler, AE ;
Janson, J ;
Bonner-Weir, S ;
Ritzel, R ;
Rizza, RA ;
Butler, PC .
DIABETES, 2003, 52 (01) :102-110
[10]   The replication of β cells in normal physiology, in disease and for therapy [J].
Butler, Peter C. ;
Meier, Juris J. ;
Butler, Alexandra E. ;
Bhushan, Anil .
NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM, 2007, 3 (11) :758-768