Loss of Liver Kinase B1 (LKB1) in Beta Cells Enhances Glucose-stimulated Insulin Secretion Despite Profound Mitochondrial Defects.
Bottom Line: However, the full spectrum of LKB1 effects and the mechanisms involved in the secretory phenotype remain incompletely understood.Surprisingly, enhanced GSIS is seen despite profound defects in mitochondrial structure and function in LKB1-deficient β cells, expected to greatly diminish insulin secretion via the classic triggering pathway.This study shows that β cells can be manipulated to enhance GSIS to supra-normal levels even in the face of defective mitochondria and without deterioration over months.
Affiliation: From the Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.Show MeSH
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Mentions: We and others have previously shown that GSIS is enhanced after Cre-mediated deletion of LKB1 in β cells in vivo (23–25, 30). These observations were mostly obtained a short time after deletion of LKB1. To test if hyperfunctionality of β cells in βLKB mice declines with age, as seen in human type 2 diabetes and in some mouse models exhibiting enhanced insulin secretion (39), we measured glucose tolerance and serum insulin levels in βLKB mice up to 16 months after deletion. Injected glucose was cleared faster in mutant mice (Fig. 1A) along with greater insulin secretion (Fig. 1B). Thus deletion of LKB1 in β cells causes a persistent enhancement of β cell function.
Affiliation: From the Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.