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: Tamoxifen (Sigma, 20 mg/ml in corn oil) was injected subcutaneously to adult mice (1–2 months old). Two daily doses of 8 mg were used to achieve near total deletion of LKB1 in β cells, and animals were studied 2–16 months later. Because recombination occurred in utero in Ins1-Cre;LKB1lox/lox mice (30), these animals were used at younger ages (8–12 weeks) as indicated in Fig. 4. Glyburide and Nifedipine were injected intraperitoneally at the indicated doses. Measurements of blood glucose and serum insulin were performed as described elsewhere (31). The joint ethics committee (Institutional Animal Care and Use Committees) of the Hebrew University and Hadassah Medical Center and the United Kingdom Home Office (PPL 70/06608) approved the study protocol for animal welfare. The Hebrew University is an AAALAC International-accredited institute.
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.