Jiro Takemura

Islet Amyloid Polypeptide Response to Glucose, Insulin, and Somatostatin Analogue Administration

We determined islet amyloid polypeptide (IAPP) response in plasma to oral and intravenous glucose administration and intravenous insulin injection in nondiabetic subjects. Moreover, we studied the effect of somatostatin analogue SMS 201-995 on glucose-induced IAPP secretion in nondiabetic subjects. Plasma IAPP concentration was determined by radioimmunoassay. Oral administration of 75 g glucose (n = 8) significantly increased plasma IAPP levels from 4.5 ± 0.7 to 14.0 ± 1.7 pM (P < 0.01) 60 min after administration. Intravenous administration of 10 g glucose (n = 7) also caused a significant increase in plasma IAPP from 5.0 ± 0.4 to 11.6 ± 0.9 pM (P < 0.01) 5 min after injection. Plasma IAPP significantly decreased from 5.1 ± 0.4 to 2.9 ± 0.4 pM (P < 0.01) 60 min after intravenous insulin injection (n = 8). Pretreatment with SMS 201-995 completely abolished IAPP and insulin secretion to intravenous glucose injection. A significant correlation was found between plasma IAPP and insulin levels in oral and intravenous glucose administration and between plasma IAPP and C-peptide levels during insulin-induced hypoglycemia. These results suggest that IAPP is cosecreted with insulin in response to a glucose load and secretion of IAPP is inhibited by hypoglycemia and somatostatin. IAPP may serve as a novel pancreatic hormone to control carbohydrate metabolism.

Effect of 1, 25-dihydroxyvitamin D3 on pancreatic B and D cell function

To investigate the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on pancreatic B and D cell function in normal rats, 1 microgram of 1,25(OH)2D3 was administered intravenously 20 hours before the experiment. The plasma 1,25(OH)2D3 and calcium concentrations were significantly elevated, and plasma insulin levels also increased in 1,25(OH)2D3-administered rats compared with controls. Glucose-induced insulin and somatostatin release from the isolated pancreas perfused with lower calcium, however, was the same between the 1,25(OH)2D3-administered group and the controls. On the other hand, when the isolated pancreas was perfused with higher calcium, the glucose-induced insulin release was significantly increased in the 1,25(OH)2D3-administered group, while no significant difference in somatostatin release was observed in any group. These results suggest that the sensitivity of pancreatic B cells to glucose perfused with more calcium may increase when 1,25(OH)2D3 has been previously administered. In addition, 1,25(OH)2D3 does not seem to affect the somatostatin release from the pancreatic D cells.

Effect of truncal vagotomy on pancreatic polypeptide response after intravenous glucose administration.

Intravenous glucose infusion was performed in six dogs with and without truncal vagotomy, and plasma pancreatic polypeptide (PP) responses were compared before and after truncal vagotomy. Following truncal vagotomy, basal PP levels decreased significantly from 286 +/- 64 pg/ml (mean +/- S.E.) to 94 +/- 14 pg/ml (P less than 0.05). Basal plasma insulin and blood glucose levels also tended to be lower, but not significantly. During the infusion of glucose, blood glucose concentrations rose rapidly in both groups and after 15 min reached peak values which were not significantly different from each other. In the vagotomized group the plasma insulin response to intravenous glucose infusion was significantly lower than in the control group. Following intravenous glucose loading, plasma PP concentrations decreased rapidly in both groups, but the PP level in the vagotomized group was suppressed only to 77 +/- 4% of the basal level whereas in the control group it decreased by 45 +/- 8%, significantly lower than in the vagotomized group (P less than 0.01). These results suggest that basal PP is regulated by vagal tonus and that vagus controls, at least in part, suppression by intravenous glucose administration.

Effects of prostaglandin E2 and D2 on gastric somatostatin and gastrin secretion

The effects of PGE2 and PGD2 on gastric somatostatin and gastrin releases were investigated using the isolated perfused rat stomach. In the presence of 5.5 mM glucose, the infusion of PGE2 elicited a significant augmentation in somatostatin release, but suppressed gastrin secretion from the perfusate. On the other hand, PGD2 did not affect somatostatin release, although the gastrin secretion decreased significantly, the same as after PGE2 infusion. These results suggest that PGE2 and PGD2 may be important in the regulation of gastric endocrine function, but that PGD2 does not affect gastric somatostatin secretion.

Effect of starvation on gastric somatostatin release

Abstract The present study is an investigation of the effects of 16 and 48 hours starvation on gastric somatostatin release using the isolated perfused rat stomach. Before sacrifice the body weights and blood glucose levels of fasted rats were significantly lower than fed rats. In the presence of 4.4 mM glucose, basal somatostatin concentrations in the stomach perfusate of fasted rats were also significantly lower. Gastric somatostatin release was stimulated in all three groups similarly by 5 × 10 −8 M glucagon when the decrease in basal levels is considered. These results suggest that gastric somatostatin as well as pancreatic somatostatin contributes to nutrient homeostasis and that nutrient homeostasis influences somatostatin levels in turn.

Effect of Truncal Vagotomy on GIP Release Induced by Intraduodenal Glucose or Fat in Dogs

In order to elucidate the role of the vagus nerve in the release of gastric inhibitory polypeptide (GIP), mongrel dogs were given a 4-min intraduodenal infusion of 10 g glucose or 5 g soybean oil before and again 1 month after truncal vagotomy (TV). The basal GIP concentrations were significantly elevated after TV. The plasma GIP levels following glucose infusion in the vagotomized dogs were significantly higher than those in the untreated dogs, whereas the GIP levels following fat infusion were not affected by TV. These results suggest that TV influences glucose-induced GIP release but not fat-induced GIP release, indicating that different mechanisms of the vagus nerve may be involved in glucose- and fat-induced GIP secretions.

Effect of acetylsalicylic acid on blood glucose and glucose regulatory hormones in mild diabetes

In order to investigate the effect of acetylsalicylic acid (ASA) on glucose tolerance and glucose regulatory hormones, ASA was given to 14 diabetic patients for seven days by two different methods. A 50 g oral glucose tolerance test (OGTT) was performed before and after the treatment. Nine of 14 diabetics received a dosage of 1.5 g of ASA three times a day for seven days plus 1.5 g on the eighth day one hr before the test (group I). The other 5 patients had the same dosage of ASA as group I, but were not administered ASA prior to the second OGTT (group II). In group I the ASA treatment improved the glucose tolerance associated with sustained rise of plasma insulin significantly, whereas no significant change in glucose tolerance or plasma insulin was observed in group II compared the pretreatment level. The ASA had no significant effect on plasma glucagon or gastric inhibitory polypeptide in either group I or group II. These results suggest that ASA allievates glucose intolerance in maturity onset diabetics by a direct enhancement of insulin secretion, and, moreover, that it is important to maintain elevated ASA concentrations in their blood.

The effect of ventromedial hypothalamic nuclei destruction on somatostatin and insulin release from the isolated perfused rat pancreas

Abstract The effect of electrolytic lesions in the ventromedial hypothalamic nuclei (VMH) on somatostatin and insulin release was studied using the isolated perfused rat pancreas. Obesity gradually developed in the rats after placement of the VMH lesions, and fasting insulin levels determined immediately before the isolation of the pancreas were significantly higher than those in sham-operated controls. In the presence of 4.4 mM glucose, both perfusate somatostatin and insulin responses to arginine were significantly greater than in the controls, suggesting that VMH lesions cause not only hypersecretion of insulin but hypersecretion of somatostatin as well.

THE EVIDENCE FOR THE REGULATORY ROLE OF ENDOGENOUS GIP AS A GLUCOSE DEPENDENT INSULINOTROPIC HORMONE IN PATIENTS WITH DUODENAL ULCER

In order to investigate the mechanism of GIP secretion and the role of endogenous GIP in the enteroinsular axis in duodenal ulcer patients, we have compared plasma GIP, insulin, and blood glucose responses to oral glucose ingestion in 10 duodenal ulcer patients, 5 patients with total gastrectomy, and 20 normal subjects. The mean basal level of plasma GIP in totally gastrectomized patients was significantly higher than in normal subjects, while in duodenal ulcer patients the value was not different from that of controls. Plasma GIP and insulin responses to oral glucose loading were significantly higher than normal in both groups. The degree of exaggerated plasma GIP and insulin secretions was more prominent and earlier in totally gastrectomized patients than in duodenal ulcer patients, and was positively correlated with the blood glucose increase during glucose ingestion. On the other hand, no significant change in GIP secretion during insulin‐induced hypoglycaemia was observed in normal subjects, duodenal ulcer patients, or patients with selective proximal vagotomy. These findings indicate that the exaggerated GIP response to oral glucose in duodenal ulcer patients may be due not to increased vagal tone, but to more rapid incoming load. We found also that the hypersecretion of GIP induced by glucose ingestion in patients with duodenal ulcer and total gastrectomy may be responsible for the hyperfunction of the enteroinsular axis in these patients.

Somatostatin, glucagon, and insulin secretion from isolated perfused pancreas of new genetically obese hyperglycemic rats

Insulin, somatostatin, and glucagon release from the perfused pancreas was studied in the newly developed genetically obese hyperglycemic hyperinsulinemic (Wistar fatty) rat. Insulin and somatostatin levels rose significantly compared to those in lean littermate controls during arginine infusion. The glucagon increase, however, was significantly less when total amounts during arginine infusion were calculated. These results show that hypersecretion of insulin and somatostatin in vitro may suppress glucagon release in Wistar fatty rats.