PMID- 10102688
OWN - NLM
STAT- MEDLINE
DCOM- 19990415
LR  - 20190515
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 48
IP  - 4
DP  - 1999 Apr
TI  - Interaction between genetic and dietary factors determines beta-cell function in 
      Psammomys obesus, an animal model of type 2 diabetes.
PG  - 731-7
AB  - The gerbil Psammomys obesus develops nutrition-dependent diabetes. We studied the 
      interaction between diet and diabetic predisposition for beta-cell function. A 
      4-day high-energy (HE) diet induced a 3-, 4-, and 1.5-fold increase in serum 
      glucose, insulin, and triglycerides, respectively, in diabetes-prone (DP) but not 
      diabetes-resistant (DR) P. obesus. Hyperglycemia and concurrent 90% depletion of 
      islet immunoreactive insulin stores were partially corrected by an 18-h fast. In 
      vitro early insulin response to glucose was blunted in both DR and DP perifused 
      islets. The HE diet augmented early and late insulin response in DR islets, 
      whereas in DP islets, secretion progressively declined. Dose-response studies 
      showed a species-related increase in islet glucose sensitivity, further augmented 
      in DP P. obesus by a HE diet, concomitant with a decreased threshold for glucose 
      and a 55% reduction in maximal response. These changes were associated with a 
      fourfold increase in glucose phosphorylation capacity in DP islets. There were no 
      differences in islet glucokinase (GK) and hexokinase (HK) Km; however, GK Vmax 
      was 3.7- to 4.6-fold higher in DP islets, and HK Vmax was augmented 3.7-fold by 
      the HE diet in DP islets. We conclude that the insulin-resistant P. obesus has an 
      inherent deficiency in insulin release. In the genetically predisposed P. obesus 
      (DP), augmented islet glucose phosphorylation ability and diet-induced reduction 
      of the glucose threshold for secretion may lead to inadequate insulin secretion 
      and depletion of insulin stores in the presence of caloric abundance. Thus, 
      genetic predisposition and beta-cell maladaptation to nutritional load seem to 
      determine together the progression to overt diabetes in this species. It is 
      hypothesized that similar events may occur in obese type 2 diabetic patients.
FAU - Nesher, R
AU  - Nesher R
AD  - Department of Endocrinology and Metabolism, the Hebrew University-Hadassah 
      Medical Center, Jerusalem, Israel. nesherr@cc.huji.ac.il
FAU - Gross, D J
AU  - Gross DJ
FAU - Donath, M Y
AU  - Donath MY
FAU - Cerasi, E
AU  - Cerasi E
FAU - Kaiser, N
AU  - Kaiser N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Insulin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animal Nutritional Physiological Phenomena
MH  - Animals
MH  - Diabetes Mellitus, Type 2/blood/*physiopathology
MH  - *Diet
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Food Deprivation/physiology
MH  - Genetic Predisposition to Disease
MH  - Gerbillinae/*genetics
MH  - Glucose/metabolism/pharmacology
MH  - Insulin/blood
MH  - Islets of Langerhans/*physiopathology
MH  - Phosphorylation
EDAT- 1999/04/02 00:00
MHDA- 1999/04/02 00:01
CRDT- 1999/04/02 00:00
PHST- 1999/04/02 00:00 [pubmed]
PHST- 1999/04/02 00:01 [medline]
PHST- 1999/04/02 00:00 [entrez]
AID - 10.2337/diabetes.48.4.731 [doi]
PST - ppublish
SO  - Diabetes. 1999 Apr;48(4):731-7. doi: 10.2337/diabetes.48.4.731.