Fat-induced changes in mouse pancreatic islet insulin secretion, insulin biosynthesis and glucose metabolism.
Insulin secretion, insulin biosynthesis and islet glucose oxidation were studied in pancreatic islets isolated from fat-fed diabetic mice of both sexes. Insulin secretion from isolated islets was studied after consecutive stimulation with alpha-ketoisocaproic acid + glutamine, glucose, forskolin, and 12-O-tetradecanoylphorbol 13-acetate. Glucose-induced insulin secretion was impaired in islets from fat-fed mice. This was associated with a reduction of approximately 50% in islet glucose oxidation. Islet insulin secretion stimulated by the non-carbohydrate secretagogues tended to be higher in the fat-fed mice, but a statistically significant effect was not observed. Pancreatic insulin content was reduced by 50%, whereas the islet insulin and DNA content was unchanged after fat feeding. Proinsulin mRNA was reduced by 35% in islets from fat-fed mice, and was associated with a reduction of approximately 50% in glucose-stimulated (pro)insulin biosynthesis. It is concluded that the insulin secretory response of islets isolated from fat-fed mice is similar to the secretory pattern known from human type 2, non-insulin-dependent diabetics, and that a defect in islet glucose recognition, resulting in decreased glucose oxidation, may be responsible for the observed insulin secretory and biosynthetic defects seen after glucose stimulation.
Capito
K
K
Department of Biochemistry A, Panum Institute, University of Copenhagen, Denmark.
Hansen
S E
SE
Hedeskov
C J
CJ
Islin
H
H
Thams
P
P
D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D005973:Glutamine / Q000494:pharmacology; D006019:Glycolysis; D066298:In Vitro Techniques; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010938:Plant Oils / Q000494:pharmacology; D011384:Proinsulin / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D000074242:Sunflower Oil; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004041:Dietary Fats; D007328:Insulin; D010938:Plant Oils; D012333:RNA, Messenger; D000074242:Sunflower Oil; D005973:Glutamine; D005576:Colforsin; D011384:Proinsulin; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; C029310:lard