Acta Diabetologica

, Volume 28, Issue 3–4, pp 193–198 | Cite as

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

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


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.

Key words

Type 2, non-insulin-dependent diabetes mellitus Insulin secretion Islet glucose metabolism Insulin biosynthesis Proinsulin mRNA 


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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • K. Capito
    • 1
  • S. E. Hansen
    • 1
  • C. J. Hedeskov
    • 1
  • H. Islin
    • 1
  • P. Thams
    • 1
  1. 1.Department of Biochemistry A, The Panum InstituteUniversity of CopenhagenCopenhagen NDenmark

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