The metabolic effects of oxytocin are mediated by a uterine type of receptor and are inhibited by oxytocin antagonist and by arginine vasopressin in the dog.

Infusion of oxytocin (OT) into normal dogs, in doses which produced plasma levels of OT in the physiological range, has been shown to increase plasma levels of glucose, insulin and glucagon and increase rates of glucose production and uptake. This study sought to determine whether there was a correlation between these metabolic effects and the oxytocic potency of four less potent oxytocic analogues when infused into normal dogs. The rank order of oxytocic potency of all 4 correlated well with the rise in plasma glucose levels, and in 3 of the 4 with the rise in plasma insulin levels. An antagonist of the oxytocic effect of OT suppressed the usual OT-induced rise in plasma glucose, insulin and glucagon as well as the increased glucose production and uptake. Arginine vasopressin (AVP) infusion, which by itself did not produce any metabolic effects, blocked completely the effects of OT infusion to raise plasma glucose and insulin levels and increase glucose production and uptake. The data suggest that the metabolic effects of OT in the dog are mediated by OT receptors that are similar to those producing the oxytocic effects. Whether the inhibition by AVP of the metabolic and hormonal effects of OT occurs at the receptor or post receptor level or via other mechanisms remains to be determined.     

Oxytocin increases extrapancreatic glucagon secretion and glucose production in pancreatectomized dogs

Infusion of oxytocin into normal dogs increases plasma levels of insulin and glucagon and glucose production and uptake. To determine whether infused oxytocin also increases glucagon secretion from extrapancreatic sites, pancreatectomized dogs, off insulin for 18 hr, were infused with oxytocin and plasma glucagon, and glucose production and uptake were measured using the [6-3H]glucose primer-infusion technique. The diabetic dogs, in the control period, had elevated plasma glucose and glucagon levels, an increased rate of glucose production, and a relative decrease in glucose uptake (decreased clearance). Infusion of oxytocin (500 microU/kg/min) caused a rise in plasma glucagon and glucose levels, increased glucose production, and further decreased glucose clearance. It is concluded that oxytocin can stimulate secretion of extrapancreatic glucagon, which contributes to the increased glucose production.     

Hepatic glucagon clearance during insulin induced hypoglycemia

Studies concerning the importance of glucagon secretion in hypoglycemic counterregulation have assumed that peripheral levels of glucagon are representative of rates of pancreatic glucagon secretion. The measurement of peripheral levels of this hormone, however, may be a poor reflection of secretion rates because of glucagon's metabolism by the liver. Therefore, in order to understand the relationship between pancreatic glucagon secretion and levels of glucagon in the peripheral blood during hypoglycemia, we evaluated hepatic glucagon metabolism during insulin induced hypoglycemia. Four dogs received an insulin infusion to produce glucose levels less than 50 mg/dl for 45 minutes. In response to this, the delivery of glucagon to the liver increased from 36.7 +/- 5.9 ng/min in the baseline to 322.6 +/- 6.3 ng/min during hypoglycemia. Hepatic glucagon uptake increased proportionally from 13.6 +/- 7.2 ng/min to 103.1 +/- 28.3 ng/min and the percentage of delivered hormone that was extracted did not change (30.8 +/- 13.8% vs 32.9 +/- 11.6%). The absolute amount of glucagon metabolized by the liver was dependent on the rate of delivery and was not directly affected by plasma glucose level per se. To directly study the effect of hypoglycemia on hepatic glucagon metabolism, five dogs were given an exogenous infusion of somatostatin followed by an infusion of glucagon and then administered insulin to produce hypoglycemia. The percent of glucagon extracted by the liver (19.5 +/- 4.9% and 21.3 +/- 6.4%) was not affected by a fall in the plasma glucose level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stimulatory effect of xenin-8 on insulin and glucagon secretion in the perfused rat pancreas

Xenin is a 25-amino acid peptide of the neurotensin/xenopsin family identified in gastric mucosa as well as in a number of tissues, including the pancreas of various mammals. In healthy subjects, plasma xenin immunoreactivity increases after meals. Infusion of the synthetic peptide in dogs evokes a rise in plasma insulin and glucagon levels and stimulates exocrine pancreatic secretion. The latter effect has also been demonstrated for xenin-8, the C-terminal octapeptide of xenin. We have investigated the effect of xenin-8 on insulin, glucagon and somatostatin secretion in the perfused rat pancreas. Xenin-8 stimulated basal insulin secretion and potentiated the insulin response to glucose in a dose-dependent manner (EC(50)=0.16 nM; R(2)=0.9955). Arginine-induced insulin release was also augmented by xenin-8 (by 40%; p<0.05). Xenin-8 potentiated the glucagon responses to both arginine (by 60%; p<0.05) and carbachol (by 50%; p<0.05) and counteracted the inhibition of glucagon release induced by increasing the glucose concentration. No effect of xenin-8 on somatostatin output was observed. Our observations indicate that the reported increases in plasma insulin and glucagon levels induced by xenin represent a direct influence of this peptide on the pancreatic B and A cells.     

Indomethacin does not affect endogenous glucose production in type 2 diabetes mellitus.

In healthy subjects, basal endogenous glucose production is partly regulated by paracrine intrahepatic factors. It is currently unknown whether paracrine intrahepatic factors also influence the increased basal endogenous glucose production in patients with type 2 diabetes mellitus. Administration of indomethacin to patients with type 2 diabetes mellitus stimulates endogenous glucose production and inhibits insulin secretion. Our aim was to evaluate whether this stimulatory effect on glucose production is solely attributable to inhibition of insulin secretion. In order to do this, we administered indomethacin to 5 patients with type 2 diabetes during continuous infusion of somatostatin to block endogenous insulin and glucagon secretion and infusion of basal concentrations of insulin and glucagon in a placebo-controlled study. Endogenous glucose production was measured 3 hours after the start of the somatostatin, insulin and glucagon infusion, for 4 hours after administration of placebo/indomethacin, by primed, continuous infusion of [6,6-(2)H(2)] glucose. At the time of administration of placebo or indomethacin, there were no significant differences in plasma glucose concentrations and endogenous glucose production rates between the two experiments (16.4 +/- 2.09 mmol/l vs. 16.6 +/- 1.34 mmol/l and 17.7 +/- 1.05 micromol/kg/min and 17.0 +/- 1.06 micromol/kg/min), control vs. indomethacin). Plasma glucose concentration did not change significantly in the four hours after indomethacin or placebo administration. Endogenous glucose production in both experiments was similar after both placebo and indomethacin. Mean plasma C-peptide concentrations were all below the detection limit of the assay, reflecting adequate suppression of endogenous insulin secretion by somatostatin. There were no differences in plasma concentrations of insulin (76 +/- 5 vs. 74 +/- 4 pmol/l) and glucagon (69 +/- 8 vs. 71 +/- 6 ng/l) between the studies with levels remaining unchanged in both experiments. Plasma concentrations of cortisol, epinephrine, and norepinephrine were similar in the two studies and did not change significantly. We conclude that indomethacin stimulates endogenous glucose production in patients with type 2 diabetes mellitus by inhibition of insulin secretion.     

Insulin and glucagon secretion in rats: effects of calcitonin gene-related peptide

Immunoreactive calcitonin gene-related peptide (CGRP) has been shown to occur in intrapancreatic nerves and islet somatostatin cells in the rat. Therefore, we investigated the effects of CGRP on insulin and glucagon secretion in the rat. CGRP was infused i.v. at one of 3 dose levels (4.3, 17 or 68 pmol/min). Infusion of CGRP alone was found to elevate basal plasma levels of both insulin and glucagon. In contrast, CGRP impaired the plasma insulin responses to both glucose (7 mg/min; P less than 0.001) and arginine (8.5 mg/min; P less than 0.001), and inhibited the arginine-induced increase in plasma glucagon concentrations (P less than 0.001). Since CGRP and somatostatin are colocalized within the D-cells, we also infused CGRP and somatostatin together at equimolar dose levels (17 pmol/min), with glucose (7 mg/min). By that, the increase in plasma insulin concentrations decreased more rapidly than during infusion of either peptide alone. Since alpha 2-adrenoceptor activation is known to inhibit glucose-stimulated insulin secretion, we also infused CGRP together with the specific alpha 2-adrenoceptor antagonist yohimbine (37 nmol/min). In that way, the plasma insulin-lowering effect of CGRP was prevented. We have shown in the rat: (1) that CGRP stimulates basal insulin and glucagon secretion; (2) that CGRP inhibits stimulated insulin and glucagon secretion; (3) that CGRP and somatostatin more rapidly induce a potent inhibitory action on glucose-stimulated insulin secretion when given together; and (4) that the alpha 2-adrenoceptor antagonist, yohimbine, counteracts the inhibitory action of CGRP on glucose-stimulated insulin secretion. We suggest that CGRP is of importance for the regulation of insulin and glucagon secretion in the rat. The mechanisms behind the islet effects of CGRP can not be established by the present results, though they apparently require intact alpha 2-adrenoceptors.     

Pre-exposure to glucagon impairs glucose recovery after insulin-induced hypoglycemia in man

The effect of a two hour period of hypo- and hyperglucagonemia on a subsequent insulin-induced hypoglycemia was studied in nine healthy volunteers. Hypoglucagonemia was provoked by somatostatin (50 micrograms/h) and hyperglucagonemia by glucagon infusion (3.25 ng/kg/min) together with somatostatin, while saline alone was given as control. Hypoglycemia was induced by insulin infusion (2.4 U/h) for two hours. The hyperglycemic effect of glucagon was transient and similar nadir glucose levels were obtained in the three experiments. Preinfusion with glucagon impaired glucose recovery in spite of preserved secretion of epinephrine during restitution of blood glucose in this experiment. It is concluded, that a period of elevated glucagon levels deteriorates the restitution of blood glucose following hypoglycemia. Hyperglucagonemia, commonly apparent in poorly controlled diabetics, may therefore be of importance in explaining the impaired recovery of blood glucose seen in such patients after hypoglycemia.     

Basal insulin, glucagon, and growth hormone replacement

Conclusions drawn from the pancreatic (or islet) clamp technique (suppression of endogenous insulin, glucagon, and growth hormone secretion with somatostatin and replacement of basal hormone levels by intravenous infusion) are critically dependent on the biological appropriateness of the selected doses of the replaced hormones. To assess the appropriateness of representative doses we infused saline alone, insulin (initially 0.20 mU.kg(-1).min(-1)) alone, glucagon (1.0 ng.kg(-1).min(-1)) alone, and growth hormone (3.0 ng.kg(-1).min(-1)) alone intravenously for 4 h in 13 healthy individuals. That dose of insulin raised plasma insulin concentrations approximately threefold, suppressed glucose production, and drove plasma glucose concentrations down to subphysiological levels (65 +/- 3 mg/dl, P < 0.0001 vs. saline), resulting in nearly complete suppression of insulin secretion (P < 0.0001) and stimulation of glucagon (P = 0.0059) and epinephrine (P = 0.0009) secretion. An insulin dose of 0.15 mU.kg(-1).min(-1) caused similar effects, but a dose of 0.10 mU.kg(-1).min(-1) did not. The glucagon and growth hormone infusions did not alter plasma glucose levels or those of glucoregulatory factors. Thus, insulin "replacement" doses of 0.20 and even 0.15 mU.kg(-1).min(-1) are excessive, and conclusions drawn from the pancreatic clamp technique using such doses may need to be reassessed.     

Effects of glucosamine on insulin and glucagon secretion in dogs and ducks.

The effects of infusion of glucosamine on immunoreactive glucagon (IRG) and insulin (IRI) secretion were studied in dogs and ducks. During systemic infusion of glucosamine, hyperglycemia developed and insulin secretion was inhibited in both species. An immediate and sustained elevation of peripheral IRG levels was induced in ducks but a transient rise, detectable only in the pancreatic vein blood, was provoked in dogs. Suppression of insulin release and stimulation of glucagon release may be mediated by the inhibition of glucose utilization in beta- and alpha-cells. The very prompt response of IRG in ducks may imply that glucosamine has a specific stimulating effect on the alpha-cells of ducks. Intrapancreatic administration of glucosamine in dogs, however, failed to elicit the rise of IRG, although insulin secretion was inhibited. Thus, it is suggested that the systemic administration of glucosamine in dogs may stimulate IRG secretion by some indirect effect. In one dog, however, a sustained rise of the pancreatic vein IRG was observed. Thus, the possibility cannot be ruled out that the difference in IRG response to glucosamine in dogs and ducks is quantitative rather than qualitative. Glucagon release by glucosamine may provide an additional factor to the hyperglycemic effect of glucosamine, in addition to its effect to suppress insulin release as well as its direct inhibitory effect on glucose utilization in tissues.     

Pharmacological doses of oxytocin affect plasma hormone levels modulating glucose homeostasis in normal man

Pharmacological doses of oxytocin administered in basal conditions evoked a rapid surge in plasma glucose and glucagon levels followed by a later increase in plasma insulin and adrenaline levels. The effects of oxytocin on plasma glucagon and adrenaline levels were potentiated by hypoglycemia. When the endogenous pancreas secretion was suppressed by cyclic somatostatin (150 micrograms/h) and exogenous glucagon (3.5 micrograms/h) and insulin (0.2 mU/kg.min) were both replaced, oxytocin (0.2 U/min) evoked a transient but significant increase in plasma glucose levels suppressing the glucose infusion rate (GIR) in the first 60 min. On the contrary at higher insulin infusion rate (0.6 mU/kg.min) plasma glucose levels and GIR remained unaffected throughout the study. Oxytocin seems also to potentiate glucose-induced insulin secretion as evidenced by hyperglycemic glucose clamp. In conclusion, pharmacological doses of oxytocin seem to exert a prevalent hyperglycemic effect by a combined action at the liver site (as glycogenolytic agent) and at the endocrine pancreas (as a stimulatory agent of A cell secretion).     

Superactive somatostatin analog decreases plasma glucose and glucagon levels in diabetic rats

The action of the new analog of somatostatin, D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160), on plasma glucagon and glucose levels was evaluated in streptozotocin-diabetic rats. The effect of this analog on the insulin-induced hypoglycemia in diabetic rats was also investigated in order to evaluate the risk of exacerbating hypoglycemia. Administration of analog RC-160, in a dose of 25 micrograms/kg b. wt. SC, inhibited plasma glucagon secretion and decreased plasma glucose levels. This effect also occurred when plasma glucagon and glucose levels were first elevated by arginine infusion, 1000 mg/kg/hr for 30 min. Subcutaneous injection of regular insulin, 15 U/kg b. wt., produced hypoglycemia with a progressive increase in glucagon levels. Analog RC-160 completely suppressed the hypoglycemia-induced glucagon release for up to 150 min after injection of the analog or insulin. A greater decrease in the plasma glucose level was observed in the group treated with insulin and the analog than in the group injected only with insulin. These results indicate that somatostatin analog RC-160 can produce a marked and prolonged inhibition of glucagon release and a decrease in the plasma glucose level in diabetic rats. This analog may be useful as an adjunct to insulin in the treatment of diabetic patients, although caution should be exercised, to prevent hypoglycemia when using somatostatin analogs together with insulin.     

Maintenance of the postabsorptive plasma glucose concentration: insulin or insulin plus glucagon?

The prevalent view is that the postabsorptive plasma glucose concentration is maintained within the physiological range by the interplay of the glucose-lowering action of insulin and the glucose-raising action of glucagon. It is supported by a body of evidence derived from studies of suppression of glucagon (and insulin, among other effects) with somatostatin in animals and humans, immunoneutralization of glucagon, defective glucagon synthesis, diverse mutations, and absent or reduced glucagon receptors in animals and glucagon antagonists in cells, animals, and humans. Many of these studies are open to alternative interpretations, and some lead to seemingly contradictory conclusions. For example, immunoneutralization of glucagon lowered plasma glucose concentrations in rabbits, but administration of a glucagon antagonist did not lower plasma glucose concentrations in healthy humans. Evidence that the glycemic threshold for glucagon secretion, unlike that for insulin secretion, lies below the physiological range, and the finding that selective suppression of insulin secretion without stimulation of glucagon secretion raises fasting plasma glucose concentrations in humans underscore the primacy of insulin in the regulation of the postabsorptive plasma glucose concentration and challenge the prevalent view. The alternative view is that the postabsorptive plasma glucose concentration is maintained within the physiological range by insulin alone, specifically regulated increments and decrements in insulin, and the resulting decrements and increments in endogenous glucose production, respectively, and glucagon becomes relevant only when glucose levels drift below the physiological range. Although the balance of evidence suggests that glucagon is involved in the maintenance of euglycemia, more definitive evidence is needed, particularly in humans.     

The effect of insulin-induced hypoglycaemia on the secretion of glucagon and hepatic glucose production in pancreatectomized dogs

The concentration of plasma glucose in insulin deprived pancreatectomized dogs was decreased from the basal 385 +/- 44 to 65 +/- 12 mg/dL by the infusion of 7 mU X kg-1 X min-1 insulin. During the infusion, the plasma concentration of immunoreactive glucagon (IRG) did not change and hepatic glucose production was decreased. This is in contrast to earlier findings in alloxan diabetic dogs in which plasma IRG decreased in hypoglycaemia. The hypothesis is put forward that, in contrast to pancreatic alpha cells in which the effect of insulin prevails, neither insulin nor a decrease in the ambient concentration of glucose exerts any effect on the secretion of glucagon from extrapancreatic alpha cells.     

Motilin release by intravenous infusion of nutrients and somatostatin in conscious dogs

to investigate the regulatory mechanism of motilin release, plasma motilin was measured by radioimmunoassay in healthy dogs during the fasting state and after intravenous administration of various nutrients and somatostatin. The fasting plasma motilin levels of these dogs were found to fluctuate intermittently. Intravenous glucose loading lowered plasma motilin, but immediately after the end of the glucose infusion as abrupt rise of plasma motilin was observed. Mixed amino acids administered intravenously abruptly inhibited motilin secretion, and plasma motilin levels remained low even 45 min after the end of the infusion. On the other hand, no remarkable change in plasma motilin was noted after the fat infusion. Following somatostatin infusion, plasma motilin was significantly decreased, remaining low even 30 min after the end of the infusion. These observations led us to conclude than motilin secretion is regulated by somatostatin and by nutrients coming through intravenous routes.     

Antidiabetic action of somatostatin after oral glucose loading: due to suppression of glucagon and growth hormone or of intestinal carbohydrate absorption?

To elucidate the mechanism by which somatostatin lowers blood glucose concentration and insulin requirement following carbohydrate ingestion in insulin dependent diabetic patients (IDDM; n = 6), the amount of insulin required for the assimilation of a 50 g glucose load was determined by means of an automated glucose-controlled insulin infusion system with and without concomitant somatostatin infusion. During the 3 hour period following glucose loading plasma concentrations of glucagon and growth hormone were diminished by somatostatin, as were the rise in blood glucose and insulin requirement (4.0 +/- 1.2 U) when compared with the control study (11.3 +/- 1.5 U; p less than 0.01). With cessation of somatostatin blood glucose levels and insulin requirement rose during the following 2 hour observation period (7.5 +/- 1.2 U) but remained basal during the control study (0.7 +/- 0.6 U; p less than 0.0005). Thus the integrated amounts of insulin required for glucose hormone were temporarily suppressed by somatostatin. It is concluded that the diminished insulin requirement and delayed rise in blood glucose during somatostatin administration after an oral glucose load is not due to its "antidiabetic" action by suppressing glucagon and growth hormone release. Our findings favour inhibition of intestinal carbohydrate absorption as the determining cause for the "antidiabetic" action of somatostatin.     

Combined effects of cold and somatostatin on glucose kinetics in dogs

The role of the endocrine pancreas in glucose production (Ra), utilization (Rd), and metabolic clearance (R'd) was investigated during acute exposure to cold in normal normothermic dogs. Two ambient temperatures (TaN = +25 degrees C and TaC = -21 degrees C) were selected. At TaC, metabolic rate and glucose turnover of the shivering dogs were 4.3 and 2.4 times, respectively, higher than in dogs resting at TaN. As compared with the pre-experimental period, somatostatin infusion at TaN induced a 25% (arterial) and 34% (portal) glucagon deficiency, while insulin concentration dropped by 59% (arterial) and 74% (portal). Similar values were obtained at TaC for glucagon (39% arterial and 47% portal) and for insulin (52% arterial and 56% portal). At TaN, these simultaneous hormonal alterations provoked a slight reduction in plasma glucose concentration which levelled down to 4.4 mM. This reduction was due to a decrease in Ra, followed by a parallel decrease in Rd whereas R'd remained unchanged. At TaC, plasma glucose concentration dropped to the same level but quickly rose again during somatostatin infusion. This rise was due to a larger reduction in Rd than in Ra, accompanied by an abrupt fall in R'd. This reduction in R'd appears to be an important mechanism able to restore euglycemia during global pancreatic hormone deficiency in cold exposed dogs.     

Zinc Supplementation Does Not Affect Glucagon Response to Intravenous Glucose and Insulin Infusion in Patients with Well-Controlled Type 2 Diabetes

Glucagon dysregulation is an essential component in the pathophysiology of type 2 diabetes. Studies in vitro and in animal models have shown that zinc co-secreted with insulin suppresses glucagon secretion. Zinc supplementation improves blood glucose control in patients with type 2 diabetes, although there is little information about how zinc supplementation may affect glucagon secretion. The objective of this study was to evaluate the effect of 1-year zinc supplementation on fasting plasma glucagon concentration and in response to intravenous glucose and insulin infusion in patients with type 2 diabetes. A cross-sectional study was performed after 1-year of intervention with 30 mg/day zinc supplementation or a placebo on 28 patients with type 2 diabetes. Demographic, anthropometric, and biochemical parameters were determined. Fasting plasma glucagon and in response to intravenous glucose and insulin infusion were evaluated. Patients of both placebo and supplemented groups presented a well control of diabetes, with mean values of fasting blood glucose and glycated hemoglobin within the therapeutic goals established by ADA. No significant differences were observed in plasma glucagon concentration, glucagon/glucose ratio or glucagon/insulin ratio fasting, after glucose or after insulin infusions between placebo and supplemented groups. No significant effects of glucose or insulin infusions were observed on plasma glucagon concentration. One-year zinc supplementation did not affect fasting plasma glucagon nor response to intravenous glucose or insulin infusion in well-controlled type 2 diabetes patients with an adequate zinc status.     

Glucose regulation of arginine-induced pancreatic somatostatin release from the isolated perfused rat pancreas

The effects of glucose alone, combinations of glucose with arginine or tolbutamide and either arginine or tolbutamide alone, on somatostatin, insulin, and glucagon secretion were investigated using the isolated perfused rat pancreas. When glucose alone was raised in graded increments at 15-min intervals from an initial concentration of 0 mM to a maximum of 16.7 mM, somatostatin as well as insulin in the perfusate increased with the glucose, while glucagon decreased. The similarity of the glucose stimulated somatostatin and insulin release was especially evident when the perfusate glucose was increased from an initial dose of 4.4 mM rather than 0 mM to 8.8 mM or 16.7 mM. In addition, glucose at concentrations varying from 4.4 mM to 11 mM dose-dependently enhanced arginine-induced somatostatin and insulin release and suppressed glucagon release dose-dependently as before. Arginine in the absence of glucose was not capable of stimulating somatostatin secretion whereas tolbutamide, in contrast, was capable of stimulating somatostatin secretion even in the absence of glucose.     

Carbohydrates modulate opiate receptor mediated mechanisms during postprandial endocrine function

The present study was designed to determine the role of carbohydrates during naloxone-induced opiate receptor blockade upon the postprandial rise of plasma somatostatin (SLI), insulin and pancreatic polypeptide (PP) levels in response to protein and fat test meals in conscious dogs. Test meals consisting of 50 g liver extract + 50 g sucrose or 50 g corn oil + 50 g sucrose dissolved in 300 ml water were instilled intragastrically, respectively. Additionally, liver extract and fat meals were given with a concomitant intravenous infusion of glucose. To all test meals either naloxone (4 mg) or saline was added. The addition of sucrose to liver extract or the infusion of i.v. glucose during the liver meal abolished the inhibitory effect of naloxone on the rise of postprandial somatostatin levels which has been described recently. The addition of carbohydrate either orally or intravenously to the fat meal resulted in an even stimulatory effect of naloxone upon the rise of postprandial somatostatin levels. Insulin levels were not changed during liver extract + sucrose or i.v. glucose, respectively. When sucrose or i.v. glucose was administered together with the fat meal the addition of naloxone augmented postprandial insulin secretion. Pancreatic polypeptide (PP) release was augmented during the combination of sucrose or i.v. glucose with the fat and liver meal when naloxone was present in the meals. The present data demonstrate that the addition of carbohydrates either orally or intravenously to fat and protein meals modulates the effect of endogenous opiates in the regulation of postprandial somatostatin, insulin and pancreatic polypeptide release in dogs in a way that carbohydrates induce inhibitory mechanisms that are mediated via endogenous opiate receptors.     

Rate dependent stimulation of insulin and glucagon but not gastrin and somatostatin release during the intestinal phase of a meal

Previous studies have indicated a possible influence of gastric emptying on postprandial pancreatic endocrine function and the present study was designed to determine if the rate at which nutrients enter the small intestine may play a role in the postprandial regulation of insulin, glucagon, somatostatin and gastrin release in conscious dogs. In response to an intraduodenal instillation of a liver extract--sucrose test meal postprandial insulin and glucagon levels increased significantly with increasing infusion rates of the test meal, whereas somatostatin and gastrin levels did not change. The rise of the endocrine factors preceded any increase of peripheral vein plasma glucose levels. The present data demonstrate that during the intestinal phase of a meal the rate of nutrient entry into the duodenum favours insulin and glucagon but not somatostatin and gastrin release. This mechanism could be of importance in the regulation of nutrient homeostasis during the ingestion of certain carbohydrate containing meals.