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Linda Ahlkvist

Research project participant

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Defective insulin secretion by chronic glucagon receptor activation in glucose intolerant mice.


  • Linda Ahlkvist
  • Bilal Omar
  • Anders Valeur
  • Keld Fosgerau
  • Bo Ahrén

Summary, in English

Stimulation of insulin secretion by short-term glucagon receptor (GCGR) activation is well characterized, however, the effect of long-term GCGR activation on beta-cell function is not known, but of interest, since hyperglucagonemia occurs early during development of type 2 diabetes. Therefore, we examined whether chronic GCGR activation affects insulin secretion in glucose intolerant mice. To induce chronic GCGR activation, high-fat diet fed mice were continuously (2wk) infused with the stable glucagon analogue ZP-GA-1 and challenged with oral glucose and intravenous glucose +/- GLP-1. Islets were isolated to evaluate the insulin secretory response to glucose +/- GLP-1 and pancreases were collected for immunohistochemical analysis. Two-week ZP-GA-1 infusion reduced insulin secretion both after oral and intravenous glucose challenges in vivo and in isolated islets. These inhibitory effects were corrected for by GLP-1. Also, we observed increased beta-cell area and islet size. We conclude that induction of chronic ZP-GA-1 levels in glucose intolerant mice markedly reduces insulin secretion, and thus, we suggest that chronic activation of the GCGR may contribute to the failure of beta-cell function during development of type 2 diabetes.


  • Medicine, Lund
  • Insulin Signal Transduction
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year







Journal of Endocrinology



Document type

Journal article


Society for Endocrinology


  • Endocrinology and Diabetes



Research group

  • Insulin Signal Transduction


  • ISSN: 1479-6805