Dynamics of pancreatic ?-cell responses to glucose

Abstract

5iicroperifusion was used to study the dynamics of insulin release and metabolic changes in pancreatic islets microdissected from ob/ob-miee. When the islets were suddenly exposed to a high glucose eonccntxation, their content of glucose-6-phosphate and fructose-1, 6-diphosphate started to rise immediately, whereas a secretory response was not observed until after about 80 see. This is consistent with the hypothesis that glucose metabolism initiates insulin release. Fasting the donor animMs for 18 h reduced the initial phase of glucosestimulated release but left the rise of gtucose-6-phosphate, as well as the late phase of sustained' release, unaffected. The use of a tissue culture meditml (TCM 199) instead of Krebs-Ringer bicarbonate buffer as the basal medium increased the secretory responses to glucose, particularly the initial phase, both in islets from fed and fasted mice. However, the difference between fed and fasted mice remained. Theophylline did not restore the impaired initial secretory response after fasting. The responses of islet fruetose-l,6-diphosphate and adenosine-5-triphosphate to glucose depended on the nutritional state of the animals and on the type of basal medium. No consistent correlation was observed between the changes of these substrates and the dynamics of insulin release.

Insulin release and cyclic AMP accumulation in response to glucose in pancreatic islets of fed and starved rats.

“…Inhibition of the phosphodiesterases with IBMX did not fully restore the impaired glucose-stimulated insulin response in starved islets, as reported by others (11,39). However, IBMX amplified the dose-dependent effects of glucose similarly in fed and starved islets, and the sensitivity of insulin re-…”

“…It is well documented in all species thus far studied, in vivo (1)(2)(3)(4)(5)(6)(7) and in vitro (8)(9)(10)(11)(12)(13), that starvation results in an impairment of glucose-stimulated insulin secretion. This impairment is not complete, rather there is a decreased sensitivity to glucose of the insulin secretory mechanism (10,14,15), and glucose refeeding in vivo (2,4,7,16), or in vitro (15) has been reported to overcome this defect.…”

“…However, other reports suggest that a defect in cyclic AMP generation, rather than in carbohydrate metabolism, might be responsible for the decreased insulin release observed in starvation. Thus, fasting ob/ob mice for 18 h reduced the initial phase of glucose-induced insulin release, but left the rise of glucose-6-phosphate unaffected (11); and the glucoseinduced increase of cyclic AMP was reduced by 50% in islets of rats starved for 24 h, whereas glucose oxidation was not affected (41).…”

Further Studies on 5‐hydroxytryptamine Transport in Pancreatic Islets and Isolated Β‐cells

“…It has also been demonstrated, by ultracytochemical techniques, that stimulation of insulin secretion by glucose increases the incorporation of peroxidase in a vesicular pool in the /3-cells (Orci, Malaisse-Lagae, Ravazzola, Amherdt & Renold, 1973). Against this background, we tested the effect of glucose and theophylline on the islet uptake of labelled 5-HT; glucose being an effective secretagogue of insulin release from ,8-cells of ob/obmice (Lernmark, 1971b) and theophylline a poten- tiator of that release (Idahl, 1973). Figure 2 shows that 20 mM D-glucose and 5 mm theophylline had no effect on the uptake of 1.5 FM 5-HT, either when the incubation time was 5 min (apparent initial uptake) or 120 min (net uptake).…”

Isolated mouse pancreatic β-cells show cell-specific temporal response pattern

“…Normally, glucose-induced firstphase insulin release from ob/ob mouse islets is delivered within 1-3 min (21,23). This time period seems to overlap the period in which the majority of the ␤-cells in this study react to a glucose challenge (Fig.…”