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Oct 12, 2018

Inhibition of VDAC1 Prevents Type 2 Diabetes in Mice

Posted by in category: biotech/medical

Scientists at Lund University, Sweden showed that it is possible to prevent type 2 diabetes in mice by inhibiting a protein known as VDAC1. This inhibitor might be employed in treating this disease in humans [1].

Abstract

Type 2 diabetes (T2D) develops after years of prediabetes during which high glucose (glucotoxicity) impairs insulin secretion. We report that the ATP conducting mitochondrial outer membrane voltage dependent anion channel-1 (VDAC1) is upregulated in islets from T2D and non-diabetic organ donors under glucotoxic conditions. This is caused by a glucotoxicity-induced transcriptional program, triggered during years of prediabetes with suboptimal blood glucose control. Metformin counteracts VDAC1 induction. VDAC1 overexpression causes its mistargeting to the plasma membrane of the insulin secreting β cells with loss of the crucial metabolic coupling factor ATP. VDAC1 antibodies and inhibitors prevent ATP loss. Through direct inhibition of VDAC1 conductance, metformin, like specific VDAC1 inhibitors and antibodies, restores the impaired generation of ATP and glucose-stimulated insulin secretion in T2D islets.

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