Long-lasting effects of exendin-4 on insulin release and cell signaling in mice fed a high-fat diet

GLP-1 receptor activation increased glucose-stimulated insulin secretion by 100% in islets from high-fat diet-fed mice after 2 weeks of treatment with exendin-4.

• Islets from high-fat diet-fed mice showed reduced glucose responsiveness due to increased basal insulin secretion compared to control mice.
• Exendin-4 treatment significantly enhanced glucose-stimulated insulin secretion, measured at 0.124 ng/h per islet, compared to 0.062 ng/h per islet in untreated mice.
• The insulin response to forskolin was also increased in exendin-4-treated mice, showing 2.7 ng/h per islet versus 2.0 ng/h per islet in untreated mice.
• Exendin-4 treatment resulted in increased expression of the active form of protein kinase A, while the regulatory form decreased.
• No changes were observed in markers of beta-cell proliferation or apoptosis after exendin-4 treatment.

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