Across the DO mice, the expression of was negatively correlated with glucose-stimulated insulin secretion

Across the DO mice, the expression of was negatively correlated with glucose-stimulated insulin secretion. G; KCl (40 mM) plus 3.3 mM G; GLP1 (100 nM) plus 8.3 mM G; and the fatty acid (PA) palmitate (0.5 mM) plus 16.7 mM G. Efonidipine hydrochloride monoethanolate Heatmap illustrates the amount of insulin secreted into the medium for each condition. Mice are ordered by the median value of their insulin secretory responses to the 7 conditions, highlighting mice that exhibited low (left side) versus high (right side) secretory capacity. Insulin secretion values are the geometric mean of 6 individual measurements/condition/mouse for 479 DO mice, yielding a total of approximately 20,000 measures. Ordering the mice by their median response to all 7 insulin secretion conditions revealed a easy transition from mice that generally showed a poor secretory response, Efonidipine hydrochloride monoethanolate to mice that were highly responsive to all conditions. Male mice tended to belong to the highly responsive group; the 25 mice with the highest secretory response were all male (Physique 1). Under all test conditions, islets from male mice secreted more insulin than did islets from female mice (Supplemental Physique 1; supplemental material available online with this short article; The sex difference was best in response to GLP1, where males secreted approximately 3-fold more insulin than females. In 365 DO mice, we measured glucagon secretion in response to KCl plus 3 mM glucose (Supplemental Physique 1). A greater than 10-fold range in glucagon secretion was observed among the mice, Rabbit Polyclonal to CRHR2 from about 2 pg/islet to about 33 pg/islet, and on Efonidipine hydrochloride monoethanolate average was approximately 50% greater in islets from female than male mice ( 3 10C7). KCl-induced glucagon secretion was only weakly correlated with KCl-induced insulin secretion (~ 0.19), despite both measurements deriving from your same islet samples in response to the same stimulus. This Efonidipine hydrochloride monoethanolate suggests that the gene loci and molecular components that mediate the KCl-induced access of Ca2+ ions and mobilization and exocytosis of glucagon granules in cells are unique from those that mediate that for insulin granules in cells. Prior to collecting islets for the ex lover vivo secretion measurements, we measured several whole-body physiological characteristics in all of the mice (10). These characteristics included an oral glucose tolerance test (oGTT), homeostatic model assessments (HOMA) for insulin resistance (IR) and pancreatic cell function (B), steps of plasma glucose, insulin, and triglyceride (TG), and body weight at 6, 10, and 14 weeks of age, quantity of islets isolated per mouse, and the total islet insulin content. In addition, we measured total islet glucagon content, body weight, plasma glucose, insulin, and TG when the mice were euthanized (Supplemental Physique 2). Fasting plasma glucose at the age the mice were euthanized (22C26 weeks) exceeded 300 mg/dL in only 7 of 483 mice, all male. In summary, a large dynamic range was observed for all those phenotypes measured among the mice, most of which were strongly influenced by sex. That the vast majority of the DO mice were not diabetic indicates that these phenotypes are linked to genetic variance among the mice, and are not a result of diabetes. We asked if the whole-body physiological phenotypes were correlated with the insulin and glucagon secretion phenotypes from your isolated islets. Because of the strong sex bias observed in both units of characteristics, we computed the pairwise Pearsons correlations between all characteristics separately in females and males (Supplemental Physique 3). The insulin secretion responses evoked by each of the 7 conditions were positively intercorrelated. For example, secretion in response to aa or GLP1 was strongly correlated (~ 0.9) with secretion in response to 8.3 mM glucose in both male and female mice. Similarly, PA-induced insulin secretion correlated with 16.7 mM glucose (~ 0.8) and KCl-induced secretion correlated.