Enhanced Insulin Release in GK Rats with Forskolin and Mutations in AC-III Gene

What is it about?

The GK rat model of type 2 diabetes has decreased insulin release in response to glucose, which can be restored by forskolin. Forskolin does this by increasing cAMP generation and is linked to overexpression of AC-III mRNA due to two functional point mutations in the AC-III gene promoter. This study was conducted to determine the molecular mechanisms of the enhanced insulinotropic response of forskolin in GK islets.

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Why is it important?

This research is important because it helps to understand the mechanisms underlying type 2 diabetes and how it affects insulin release. The study focuses on the GK rat, a nonobese rodent model of type 2 diabetes, and demonstrates how the insulinotropic effect of forskolin in the GK rat is due to increased generation of cAMP and is associated with overexpression of adenylyl cyclase (AC)-III mRNA and gene mutations. This research contributes to the understanding of the central defect in type 2 diabetes, which is an impaired insulin response to glucose stimulation. Key Takeaways: 1. The GK rat is a lean spontaneous animal model of type 2 diabetes with a central defect in insulin response to glucose stimulation. 2. Forskolin restores the impaired insulin release in islets of the GK rat through enhanced cAMP generation, which is linked to overexpression of AC-III mRNA in GK islets due to two functional point mutations in the promoter region of the AC-III gene. 3. The study demonstrates the molecular mechanisms mediating the enhanced insulinotropic response of forskolin in GK islets.