Insulin Response to an Intravenous Glucose Load During Development of Obesity in Gold Thioglucose-Injected Mice

Abstract

The insulin secretory response to an intravenous glucose load was examined in chronically catheterized, conscious mice 2, 5, and 10 wk after induction of obesity by a single injection of gold thioglucose. At 2 wk after administration of gold thioglucose, a significant increase in both the insulinemia and incremental area under the curve of insulin release after intravenous glucose were observed (incremental area under the curve for 2-wk control mice, 852 +/- 54 min/pM; incremental area under the curve for 2-wk GTG-injected mice, 1140 +/- 114 min/pM; P < 0.05). At this stage, no significant difference existed in the glucose tolerance or body weight of control and gold thioglucose-injected mice. By 5 wk, the gold thioglucose-injected mice were approximately 33% heavier than their lean controls and showed a marked glucose intolerance. This was accompanied by overt hyperinsulinemia in both the basal state and also in response to an intravenous glucose bolus as indicated by the increase in the incremental area under the curve of insulin (5-wk control mice, 816 +/- 114 min/pM; 5-wk gold thioglucose-injected mice, 1374 +/- 156 min/pM; P < 0.05). At 10 wk after gold thioglucose administration, body weight and the degree of glucose intolerance were increased. Although 10-wk gold thioglucose-injected mice showed basal hyperinsulinemia, an intravenous glucose bolus elicited a smaller insulin secretory response than that observed in the age-matched lean control animals (10-wk control mice, 672 +/- 54 min/pM; 10-wk gold-thioglucose-injected mice 186 +/- 42 min/pM; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin Secretion and Acetylcholinesterase Activity in Monosodium <i>L</i>-Glutamate-Induced Obese Mice

“…Ninety-day-old MSG-obese mice presented moderate glycemia and severe hyperinsulinemia, already shown by other researchers [9, 35]. Hyperinsulinemia is a common phenomenon to several obesities caused by hypothalamic injuries [9, 10, 11, 12, 13, 35, 36]. The pancreatic islets isolated from MSG-obese mice disclose high insulin secretion when perifused with glucose 5.6 m M , which is held to be a blood glucose concentration before food intake [32].…”

“…However, islets from MSG-obese mice were able to increase the overall insulin secretion 14 times from 5.6 to 16.7 m M glucose perifusion, while islets from control mice increased to 28 times. Gold thioglucose-obese mice presented hyperinsulinemia during fasting and a reduced insulinemia after receiving a glucose load [36]. Obese animals presented a very small enhancement on fast glycemia and very high hyperinsulinemia, a fact that may indicate resistance to insulin action on peripheric tissues.…”

Glucose tolerance and insulin secretion after adrenalectomy in mice made obese with gold thioglucose

“…At 4 weeks after injection, GTG and control mice were anaesthetized and a chronic jugular catheter was implanted as previously described (Blair et al 1993). On completion of the catheterization procedure, and whilst still anaesthe¬ tized, half the GTG and control mice were subjected to bilateral ADX.…”

“…The procedure for conducting the i.v. GTT was as described previously (Blair et al 1993). In brief, a 100 µ fasting blood sample was collected from the indwelling jugu¬ lar catheter prior to infusion of a glucose load.…”

“…An enhanced insulin secretory response to an intravenous glucose challenge is evident at 2 weeks after administration of GTG, demon¬ strating increased insulin release at an early stage in the development of obesity (Blair et al 1993). Since insulin is a potent stimulator of lipogenesis, the increased lipid synthesis that occurs in liver and adipose tissues during the initial stages of obesity in GTG-injected mice (Cooney et al 1989, Blair et al 1991) may be the result of the stimulatory effects of inappropriate release of insulin.…”