Effect of high dietary fat on insulin secretion in genetically diabetic Goto-Kakizaki rats.
OBJECTIVE
To clarify the effects of a high fat-diet on insulin secretion from genetically diabetic beta cells, Goto-Kakizaki rats and Wistar rats were subjected to oral glucose tolerance test (OGTT) after 12-week high-fat feeding.


METHODS
We compared Wistar and Goto-Kakizaki (GK) rats fed a high-fat diet (45% fat content) for 12 weeks, measuring insulin secretion and insulin release.


RESULTS
Insulin secretion during oral glucose tolerance test (OGTT) was enhanced in high-fat diet-fed Wistar rats (WF) with normal glucose tolerance. Insulin secretion in high-fat diet-fed GK rats (GF) during OGTT also was enhanced together with deteriorated glucose tolerance. Basal insulin release from the isolated perfused pancreas at 3.3 m glucose in WF was comparable to that in normal chow-fed Wistar rats (WN), but basal insulin release in GF was remarkably higher than in normal chow-fed GK rats (GN). Stimulated insulin release induced by 16.7 m glucose was remarkably increased in WF compared with WN. Total insulin release at 16.7 m glucose in both GK rat groups was similar and minimal.


CONCLUSIONS
These results indicate that normal pancreatic beta-cells have the ability to secrete sufficient insulin to compensate for the insulin resistance induced by a high-fat diet. In contrast, glucose metabolism in diabetic rats after high-fat diet deteriorated partly because of insufficient insulin secretion caused by genetic defects and lipotoxicity due to chronically high FFA levels.
Shang
Wenbin
W
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yasuda
Koichiro
K
Takahashi
Akira
A
Hamasaki
Akihiro
A
Takehiro
Mihoko
M
Nabe
Koichiro
K
Zhou
Heying
H
Naito
Rei
R
Fujiwara
Hideya
H
Shimono
Dai
D
Ueno
Hiroyuki
H
Ikeda
Hiroki
H
Toyoda
Kentaro
K
Yamada
Yuichiro
Y
Kurose
Takeshi
T
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D046508:Culture Techniques; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D004041:Dietary Fats / Q000494:pharmacology*; D005227:Fatty Acids / Q000097:blood; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D020738:Leptin / Q000097:blood; D010179:Pancreas / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004041:Dietary Fats; D005227:Fatty Acids; D007328:Insulin; D020738:Leptin; D014280:Triglycerides; D005947:Glucose