Figure 4.

Lamtor1 deficiency increases insulin secretion but impairs mitochondrial function. (A) Insulin levels measured during the perifusion of isolated islets. Lamtor1-deficient islets secrete higher levels of insulin than the control under 16.7 mM glucose stimulation, and administration of 100 µM diazoxide eliminates this difference; however, the addition of 30 mM KCl causes a second peak in insulin secretion. (B) Insulin secretion followed by glyburide treatment. 1 µM glyburide induces higher levels of insulin secretion from Lamtor1-deficient islets, under both low and high glucose conditions. (C) Glucose-stimulated insulin secretion from perifused islets treated with nifedipine. Black and pink lines; nifedipine was added before high glucose. Blue and red lines; nifedipine was added 15 min after the addition of high glucose. Data are shown as mean ± SD. ^*P<0.05, ^**P<0.01, n=6. (D) Adenosine triphosphate levels of islets responsive to basal and high glucose (16.7 mM). ^*P<0.05. (E) Basal OCR measured by the Seahorse XF24 analyzer in the presence of 2.8 mM glucose. n=6. (F) OCR measured over a time period of 180 min. Glucose (20 mM), FCCP (1 µM) and rotenone plus antimycin A (5 µM each) were added at the indicated times. Día, diazoxide; Nif, nifedipine; ATP, adenosine triphosphate; OCR, oxygen consumption rate; FCCP, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone; R/A, rotenone plus antimycin A; NS, no significance.