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Fat-induced changes in mouse pancreatic islet insulin secretion, insulin biosynthesis and glucose metabolism

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Abstract

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 α-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.

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Authors and Affiliations

  1. Department of Biochemistry A, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark

    K. Capito, S. E. Hansen, C. J. Hedeskov, H. Islin & P. Thams

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  1. K. Capito
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  2. S. E. Hansen
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  3. C. J. Hedeskov
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  4. H. Islin
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  5. P. Thams
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Capito, K., Hansen, S.E., Hedeskov, C.J. et al. Fat-induced changes in mouse pancreatic islet insulin secretion, insulin biosynthesis and glucose metabolism. Acta Diabetol 28, 193–198 (1992). https://doi.org/10.1007/BF00778997

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