Developmental regulation of amylin and insulin-gene expression in lean (Fa/Fa) and obese (fa/fa) Zucker rats.
Obese individuals are hyperinsulinemic and insulin resistant. Because amylin is cosecreted with insulin and may contribute to the insulin resistance of obesity, this study tested the hypothesis that insulin and amylin genes are coordinately regulated by obesity and carbohydrate feeding. Insulin and amylin gene expression were measured during the suckling/weaning transition in lean (Fa/Fa) and obese (fa/fa) Zucker rats, a period associated with marked changes in tissue insulin sensitivity. There was a decline in insulin mRNA (-90 +/- 15%, P less than 0.01) and amylin mRNA (-72 +/- 21%, P less than 0.01) content in pancreases of lean rats maintained on a high-fat diet from days 15 to 30, probably reflecting the relative increase in exocrine/endocrine development during this neonatal period and the effects of fat feeding. Weaning on high-carbohydrate versus high-fat diets resulted in enhanced expression of both insulin (P less than 0.05) and amylin (P less than 0.05) mRNAs. In contrast to the decline in pancreatic insulin and amylin mRNA content observed in lean rats, there was an increase in insulin mRNA (421.3 +/- 57.5%, P less than 0.05) and no change in amylin mRNA in obese rats maintained on a high-fat diet from days 15 to 30. There was no enhancement of insulin or amylin gene expression in obese rats with high carbohydrate relative to high-fat feeding, perhaps reflecting maximum rates of transcription in these obese insulin-resistant rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Koranyi
L
L
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Tanizawa
Y
Y
Penicaud
L
L
Atef
N
N
Girard
J
J
Permutt
M A
MA
D000375:Aging; D000682:Amyloid / Q000235:genetics*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015342:DNA Probes; D005786:Gene Expression Regulation; D005838:Genotype; D007328:Insulin / Q000097:blood / Q000235:genetics*; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000254:growth & development / Q000502:physiology / Q000503:physiopathology; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D010179:Pancreas / Q000254:growth & development* / Q000502:physiology / Q000503:physiopathology; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D015347:RNA Probes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker / Q000235:genetics*
D000682:Amyloid; D001786:Blood Glucose; D015342:DNA Probes; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D015347:RNA Probes; D012333:RNA, Messenger; D012313:RNA; D004247:DNA