Impaired insulin release in aging rats: Metabolic and ionic events

We investigated the effect of aging on glucose uptake, glucose-induced O₂ consumption, glucose-induced⁴⁵Ca movements, and calmodulin content to elucidate age-related impairment of glucose-induced insulin release in pancreatic islets of Wistar rats. Intact pancreatic islets from old (24-month-old) rats showed impaired glucose-induced insulin release; glucose uptake and O₂ consumption were lower in old than in young (2-month-old) or adult (12-month-old) rats. Moreover,⁴⁵Ca uptake and calmodulin content were decreased in pancreatic islets from older rats, which explained the impairment in glucose-induced insulin release in aging. No major differences between the 3 age groups in glucose-induced⁴⁵Ca efflux in pancreatic islets were observed.     

Effect of a restricted diet on the in vitro glucose-induced insulin release of aging rats.

To study the effect of a sudden loss of body weight on the beta-cell function of aging rats, basal and glucose-induced insulin secretion was measured in pancreatic islets obtained from young (2-month-old), adult (12-month-old) and aging (24-month-old) rats, either fed ad libitum or fed a restricted diet (50% caloric restriction). Basal insulin secretion was similar in islets of young, adult and older rats. Glucose stimulated insulin release was significantly reduced in aging rats as compared to young animals. Animals fed a restricted diet showed a prolonged and higher secretory rate during first phase release when compared to animals fed ad libitum.     

Effect of phosphate omission on glucose-induced insulin release in vitro

Summary In the isolated perfused rat pancreas, omission of extracellular phosphate (H₂PO ₄ ^– significantly reduces the insulin secretion in response to 16.7 mM glucose.     

Effect of phosphate omission on glucose-induced insulin release in vitro.

In the isolated perfused rat pancreas, omission of extracellular phosphate (H2PO-4) significantly reduces the insulin secretion in response to 16.7 mM glucose.     

The role of phosphoenolpyruvate in insulin secretion: the effect of L-phenylalanine

Summary Incubation of rat islets with phenylalanine increased the tissue content of phosophoenolpyruvate, both in the presence and in the absence of glucose. At the same time, L-phenylalanine neither stimulated nor inhibited insulin release. It is unlikely that insulin secretion is tightly coupled to the availability of phosphoenolpyruvate in rat islets.     

The effect of cyproheptadine on insulin biosynthesis

Summary The effect of a potent antiserotonin-antithistaminic compound, cyproheptadine (CPH) on insulin biosynthesis was studied in pancreatic islets isolated from CPH-treated rats. Though insulin content of islets was markedly reduced in CPH-treated rats, the incorporation of radiolabeled leucine into proinsulin and insulin fractions was not affected with respect to the rate and amount. It is concluded that CPH may deplete insulin content of the islets through causing the leakage of insulin.     

Partial pancreatectomy in rats causes an impairment of the glucose-induced stimulation of pancreatic islet blood flow

Summary Adult rats were subjected to either a sham operation (S-rats) or a 60% partial pancreatectomy (P-rats). Both P- and S-rats were normoglycemic and normoinsulinemic after surgery. Four weeks later, the animals were injected i.v. with 1 ml of either 0.9% (w/v) saline or 30% (w/v) D-glucose, and after 5 min whole pancreatic blood flow (PBF) and islet blood flow (IBF) were measured, using a microsphere technique. In the saline-injected P-rats both PBF and IBF values were, higher than in S-rats (p<0.001 for both values). Administration of glucose had no effects on PBF in either S- or P-rats when compared to saline-injected animals. IBF was, however, markedly increased (p<0.01) by glucose in S-rats in comparison with saline-injected S-rats, whilst no difference in IBF was observed between glucose- and saline-injected P-rats. The fraction of PBF diverted through the islets (fIBF) was approximately 10% in S-rats and 20% in P-rats. Glucose increased fIBF in S-rats, but had no effect in P-rats. In conclusion, in S-rats a glucose-stimulated insulin release is accompanied by an increase in IBF, but this is not observed in P-rats.     

Effect of vincristine on glucose-induced insulin secretion in man

Summary 60 min after the injection of therapeutic doses of vincristine for cancer chemotherapy, there is a reduction of the total (40%) and of the acute phase (43%) areas of insulin secretion induced by a 5-g i.v. glucose load, and the constant of glucose utilization is reduced by 25%. No differences are observed after 3 5-g i.v. glucose loads given at hourly intervals in control subjects.Acknowledgment. The authors are grateful to Mr S. Castiglioni and to Miss Maria Luisa Fuser for their skillful technical assistance.     

Effects of pregnancy on the glucose-induced insulin release from cultivated pancreatic islets of the rat

Summary 7-day-cultured islets from pregnant Wistar rats released at 5.6 mM glucose significantly more insulin than islets from nonpregnant rats, whereas in vivo this heigthened glucose sensitivity is lost 48 h post partum.Investigations carried out as a part of the Forschungsprojekt Diabetes mellitus und Fettstoffwechselstörungen supported by the Ministry of Health of German Democratic Republic.     

Effects of pregnancy on the glucose-induced insulin release from cultivated pancreatic islets of the rat.

7-day-cultured islets from pregnant Wistar rats released at 5.6 mM glucose significantly more insulin than islets from nonpregnant rats, whereas in vivo this heigthened glucose sensitivity is lost 48 h post partum.     

Effect of insulin on the synthesis and release of lipid peroxide by cultured hepatocytes isolated from normal and diabetic rats

Lipid peroxide content in hepatocytes isolated from ketotic diabetic rats was higher than normal, and the release of peroxide into the media was also elevated for the initial 18 h. Insulin suppressed both peroxide release and synthesis by cultured hepatocytes isolated from normal and from diabetic rats.     

Effect of insulin on the synthesis and release of lipid peroxide by cultured hepatocytes isolated from normal and diabetic rats

Summary Lipid peroxide content in hepatocytes isolated from ketotic diabetic rats was higher than normal, and the release of peroxide into the media was also elevated for the initial 18 h. Insulin suppressed both peroxide release and synthesis by cultured hepatocytes isolated from normal and from diabetic rats.     

Effect of feeding zinc-deficient Bengal gram (Cicer arietenum) diet to rats on the in vitro absorption of L-histidine monohydrochloride

Summary The in vitro absorption of L-histidine monohydrochloride from the duodenum was less in a group of rats fed a zinc-deficient bengal gram diet than in a group fed a zinc-supplemented bengal gram diet.     

Cationic and secretory effects of BPDZ 44 and diazoxide in rat pancreatic islets

The present study aimed at comparing the effects of low concentrations of BPDZ 44, a new pyridothiadiazine derivative, and diazoxide on⁸⁶Rb outflow,⁴⁵Ca outflow,⁴⁵Ca uptake and insulin release from rat pancreatic islets. Both drugs caused similar modifications, but the effects of BPDZ 44 on the cationic and secretory events were much more marked than those of diazoxide. It is suggested that BPDZ 44 could be valuable tool for further studies of the K_ATP channels.     

The effects of a substituted sulphamoyl diuretic ‘clopamide’ (DT 327) on insulin release in vitro

Résumé Un diurétique sulphamyl Brinaldix (Clopamide DT327) fut expérimenté pour savoir si on pouvait reproduire in vitro une hypoglycémie observée après injection. L'expérience fut effectuée avec des cellules isolées d'ilots et un radio-immunoessai pour mesurer la libération d'insuline. Différentes concentrations de glucose et de diurétique furent utilisées et ni inhibition ni stimulation ne furent observées dans la libération d'insuline.     

Effect of sulpiride on prolactin release by rat pituitaries in vitro

Résumé La sulpiride stimule la libération de la prolactine de l'hypophise après 4 h d'incubation. L'addition d'extraits hypothalamiques l'inhibe, mais la sulpiride ajoutée en même temps aux extraits hypothalamiques permet l'inversion de cet effet d'inhibition. Il semble evident que la sulpiride peut modifier la libération de la prolactine en agissant directement sur l'hypophise du rat, in vitro.