Regulation of glucose transport and transporter 4 (GLUT-4) in muscle and adipocytes of sucrose-fed rats: effects of N-3 poly- and monounsaturated fatty acids.

The goal of this study was to compare the short-term effects of dietary n-3 polyunsaturated (fish oil) and monounsaturated (olive oil) fatty acids on glucose transport, plasma glucose and lipid controls in a dietary insulin resistance model using sucrose-fed rats. The underlying cellular and molecular mechanisms were also determined in the muscle and adipose tissue. Male Sprague-Dawley rats (5 weeks old) were randomized for diets containing 57.5 % (w/w) sucrose and 14 % lipids as either fish oil (SF), olive oil (SO) or a mixture of standard oils (SC) for 3 weeks. A fourth control group (C) was fed a diet containing 57.5 % starch and 14 % standard oils. After three weeks on the diet, body weight was comparable in the four groups. The sucrose-fed rats were hyperglycemic and hyperinsulinemic in response to glucose load. The presence of fish oil in the sucrose diet prevented sucrose-induced hyperinsulinemia and hypertriglyceridemia, but had no effect on plasma glucose levels. Insulin-stimulated glucose transport in adipocytes increased after feeding with fish oil (p < 0.005). These modifications were associated with increased Glut-4 protein (p < 0.05) and mRNA levels in adipocytes. In the muscle, no effect was found on Glut-4 protein levels. Olive oil, however, could not bring about any improvement in plasma insulin, plasma lipids or Glut-4 protein levels. We therefore conclude that the presence of fish oil, in contrast to olive oil, prevents insulin resistance and hypertriglyceridemia in rats on a sucrose diet, and restores Glut-4 protein quantity in adipocytes but not in muscle at basal levels. Dietary regulation of Glut-4 proteins appears to be tissue specific and might depend on insulin stimulation and/or duration of dietary interventions.     

Failure of chronic hyperinsulinemia to suppress pancreatic glucagon in vivo in the rat.

To determine the effects of chronic hyperinsulinemia on glucagon release, rats were made hyperinsulinemic for 14 days by supplementation of drinking water with sucrose (10%; sucrose-fed) to increase endogenous release or by implantation of osmotic minipumps (subcutaneous, s.c.; or intraperitoneal, i.p.) to deliver exogenous insulin (6 U/day). Both s.c. and i.p. rats also had sucrose in the drinking water to prevent hypoglycemia. Plasma insulin levels were significantly elevated in sucrose-fed, s.c., and i.p. rats. However, glucose levels were significantly elevated in sucrose-fed rats only. Surprisingly, plasma glucagon concentrations were elevated in i.p. and s.c. rats and were not suppressed in sucrose-fed rats. Inverse relationships were found between the plasma levels of insulin and glucose (n = 65; r = -0.42, p less than 0.0001) and between glucose and glucagon (n = 73; r = -0.46, p less than 0.0001). However, unexpectedly, a positive correlation between insulin and glucagon (n = 65; r = 0.47, p less than 0.0001) was established. As suppression of plasma glucagon levels below basal was not observed in any of the hyperinsulinemic or hyperglycemic rats, we wished to establish further whether pancreatic glucagon release could be suppressed below basal levels in the rat by another means. Thus, high doses of somatostatin (50-100 micrograms.kg-1.min-1) were infused for 45 min into normal rats without or with a concomitant hyperinsulinemic, hyperglycemic glucose clamp. Somatostatin fully suppressed insulin, but although plasma glucagon levels were decreased by somatostatin infusion relative to saline-infused animals, there was still no suppression below basal levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sucrose feeding effects inhibition of gamma-glutamyltranspeptidase in the liver of the rat: possible mediation by thyroid hormone

The effect of sucrose on Fischer 344 rat liver gamma-glutamyltranspeptidase (gammaGT) was studied: in adults fed sucrose for 3 weeks; and rats exposed to sucrose from the 18th day of gestation to the 40th day after birth. Rats fed regular rodent chow served as controls. Sucrose caused mild lipemia; and in the liver an increase in size and fat build-up without damage. In adult sucrose-fed rats, compared to controls, plasma glucose levels were increased: 1.12-, 1.40- and 1.13-fold after 24, 48h and 3 week consumption of sucrose, respectively. Insulin levels were unaltered for the first week of sucrose consumption but increased from control levels: 16% at 1 week, and 2.0-fold at 3 weeks. The T3 levels were comparable to control levels 24h after the sucrose was started and were increased: 1.22-, 1.13- and 1.12-fold at 48h, 1 and 3 weeks, respectively. The T4 levels were comparable at all time points between sucrose-fed and control rats. Liver gammaGT activity exhibited a steady decrease from control levels: after 24, 48h, 1 and 3 weeks of sucrose feeding the decrease was 5, 8, 21 and 37%, respectively in homogenates; and 10, 17, 24 and 41%, respectively in plasma membranes. Perinatal sucrose exposure effected in 40-day-old rats, compared controls: a 1.09-fold increase in plasma glucose; no change in plasma insulin; an increase of 1.15- and 1.39-fold in plasma levels of total and free T3, respectively; a decrease of 20 and 14% in plasma levels of total and free T4, respectively. gammaGT activity was decreased in liver plasma membranes isolated from sucrose-exposed rats relative to those of control: 80% in the male; 82% in the female. Relative specific activities of gammaGT were the same in both males: 15.4 and 16.1 in control and sucrose-exposed male rats, respectively; and females: 14.1 and 15.4 in control and sucrose-exposed female rats, respectively. gammaGT was 2-fold higher in the livers of female relative to male rats in sucrose-exposed and control groups. Kidney gammaGT activities were the same in control and sucrose-exposed rats. The involvement of T3 in the sucrose-induced decrease in liver gammaGT is discussed.     

Probucol attenuated hyperglycemia in multiple low-dose streptozotocin-induced diabetic mice.

The present studies were undertaken to examine the effects of probucol on the protection against pancreatic beta-cell damage by multiple low-dose streptozotocin (STZ: 40 mg/kg, ip). The degree of hyperglycemia at 7, 14 and 17 days after STZ injection was attenuated by probucol. Serum immunoreactive insulin (IRI) levels were increased in the rats fed probucol containing diet at Day 14 and 17. Serum IRI levels after intraperitoneal injection of 2.0 g/kg glucose was reduced in STZ mice and the reduction of serum IRI levels was attenuated in the rats fed probucol, accompanied with a significant reduction of the degree of hyperglycemia after bolus of glucose. Probucol attenuated the reduction of pancreatic IRI content by STZ. The percentage of Thy 1.2-positive splenocytes was increased by STZ and probucol reduced the percentage of Thy 1.2-positive splenocytes, although there were no differences in the populations of splenocytes, positive with Lyt 2 or L3/T4. These data suggest that probucol has a protective action against pancreatic insulitis by multiple low-dose STZ administration.     

Insulin and glucagon secretion and the insulin sensitivity of peripheric organs of colony-bred sand rats fed with pellet diet after weaning.

Colony-bred sand rats were fed with rat pellet chow in restricted quantities or ad libitum for 8--10 or 28--31 weeks after weaning. The changes of glucose metabolism were characterized by an intraperitoneal glucose tolerance test. The daily food intake and the average weight gain differed only in the first 5--7 weeks of pellet nutrition. In the impaired glucose tolerance tests of all sand rats the high basal plasma IRI levels were not significantly increased by the grossly enhanced blood glucose concentrations. The insulin secretion of either acutely incubated or for 8 days cultivated isolated pancreatic islets, however, was stimulated already by low (1.7 and 5 mM) glucose concentrations in all diet groups. Otherwise the glucagon secretion of isolated islets was not suppressed by high glucose concentrations. No changes of insulin or glucagon contents of islets were found in the different diet groups. The adipocytes of all animals revealed a complete ineffectiveness of insulin on the glucose utilization to CO2 and triglycerides. The basal glucose conversion to CO2 and glycogen in skeletal muscle and the stimulatory potency of insulin was low and not distinctly different in all groups. In liver glycogen and triglyceride contents as well as gluconeogenic enzyme activities were not influenced by feeding of different quantities of pellet diet at the investigated time points. The time course of the metabolic and clinical alterations demonstrates that the peripheral organs become insensitive to insulin in the first weeks after weaning.     

Running Exercise Improves Metabolic Abnormalities and Fat Accumulation in Sucrose-Induced Insulin-Resistant Rats

NARA, MAKOTO, MASAKI TAKAHASHI, TSUGIYASU KANDA, YOUNOSUKE SHIMOMURA, ISAO KOBAYASHI. Running exercise improves metabolic abnormalities and fat accumulation in sucrose-induced insulin-resistant rats. Insulin resistance and hyperinsulinemia are observed in rats fed a high sucrose diet. Insulin resistance is thought to be related to abnormal fat distribution. We previously reported the metabolic characteristics and the fat distribution in rats with sucrose-induced insulin resistance. This study was designed to examine the effects of exercise in these rats. The rats were divided into three groups: those receiving a starch-based diet (control), those receiving a high-sucrose diet (sucrose fed), and those receiving a high-sucrose diet and wheel-running exercise (exercised). Animals were killed after 4 weeks or 12 weeks. After 4 weeks, the three groups did not differ with respect to gain in adipose tissues. The portal vein (PV) insulin concentration was significantly increased in the sucrose-fed and the exercised rats compared with the control rats. The inferior vena cava (IVC) glucose concentration and the PV free fatty acid (FFA) were significantly lower in the exercised rats than in the sucrose-fed rats. After 12 weeks, the exercised rats had significantly lower mesenteric fat (MS) and subcutaneous fat (SC) and a lower MS:SC ratio than the sucrose-fed rats. The glucose levels in IVC, PV, and FFA in PV were significantly reduced in the exercised rats as compared with the sucrose-fed rats. These findings suggest that long-term exercise improves insulin resistance by reducing the accumulation of MS as well as SC. It is also suggested that short-term exercise improves glucose metabolism without change of fat accumulation.     

Insulin and glucose in neonatal calves after peroral insulin and intravenous glucose administration.

Effects of peroral insulin on plasma concentrations of immunoreactive insulin (IRI) and glucose in newborn calves were studied. Bovine insulin was administered in amounts of 0.5 mg/kg body weight immediately preceding first colostrum. Thereafter, neither an increased IRI response nor a lowering of blood glucose level were observed, indicating that insulin was either not absorbed from the intestine or possibly retained in the liver. Feeding of whole milk was followed by a higher rise in IRI and glucose concentrations than feeding of colostrum after po insulin. However, when compared with 1-3-month old calves, IRI responses to feeding and to iv infused glucose were markedly smaller on the first and second day of life respectively, while glucose responses were similar. This indicates that insulin secretory mechanisms are not fully developed in the newborn calf.     

Effect of pinealectomy on plasma glucose, insulin and glucagon levels in the rat

In an attempt to know the role of the pineal gland on glucose homeostasis, the blood plasma concentrations of glucose, insulin and glucagon under basal conditions or after the administration of nutrients were studied in the jugular vein of conscious pinealectomized (Pn), melatonin-treated pinealectomized (Pn + Mel) and control (C) rats. Glucose levels were smaller in C than in Pn rats, while immunoreactive insulin (IRI) concentrations were significantly greater in C than in Pn rats. Contrary to this, immunoreactive glucagon (IRG) levels were significantly greater in Pn than in C animals. Melatonin treatment of Pn rats induces an increase of IRI concentrations and a reduction in IRG levels. Similar changes were obtained when hormonal determinations were carried out in portal blood plasma. Although ether anesthesia increases circulating glucagon levels in the porta and cava veins, the qualitative changes of plasma insulin and glucagon in Pn and Pn + Mel were similar to those found in conscious rats. To determine the effects of nutrients on pancreatic hormone release, intravenous arginine or oral glucose were administered to the animals of the three experimental groups. In C rats, both glucose and IRI levels reached a peak 30 minutes after glucose ingestion, decreasing thereafter. However, in Pn rats a glucose intolerance was observed, with maximum glucose and insulin concentrations at 60 minutes, while in Pn + Mel animals, glucose and IRI concentrations were in between the data obtained with the other two groups. Furthermore, glucose ingestion induced a significant reduction of IRG levels in all the groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of cerebrocrast, a new long-acting compound on blood glucose and insulin levels in rats when administered before and after STZ-induced diabetes mellitus

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that is characterized by selective destruction of insulin secreting pancreatic islets beta-cells. The formation of cytokines (IL-1beta, IL-6, TNF-alpha, etc.) leads to extensive morphological damage of beta-cells, DNA fragmentation, decrease of glucose oxidation, impaired glucose-insulin secretion and decreased insulin action and proinsulin biosynthesis. We examined the protective effect of a 1,4-dihydropyridine (DHP) derivative cerebrocrast (synthesized in the Latvian Institute of Organic Synthesis) on pancreatic beta-cells in rats possessing diabetes induced with the autoimmunogenic compound streptozotocin (STZ). Cerebrocrast administration at doses of 0.05 and 0.5 mg/kg body weight (p.o.) 1 h or 3 days prior to STZ as well as at 24 and 48 h after STZ administration partially prevented pancreatic beta-cells from the toxic effects of STZ, and delayed the development of hyperglycaemia. Administration of cerebrocrast starting 48 h after STZ-induced diabetes in rats for 3 consecutive days at doses of 0.05 and 0.5 mg/kg body weight (p.o.) significantly decreased blood glucose level, and the effect remained 10 days after the last administration. Moreover, in these rats, cerebrocrast evoked an increase of serum immunoreactive insulin (IRI) level during 7 diabetic days as compared to both the control normal rats and the STZ-induced diabetic control rats. The STZ-induced diabetic rats that received cerebrocrast had a significantly high serum IRI level from the 14th to 21st diabetic days in comparison with the STZ-induced diabetic control.The IRI level in serum as well as the glucose disposal rate were significantly increased after stimulation of pancreatic beta-cells with glucose in normal rats that received cerebrocrast, administered 60 min before glucose. Glucose disposal rate in STZ-induced diabetic rats as a result of cerebrocrast administration was also increased in comparison with STZ-diabetic control rats. Administration of cerebrocrast in combination with insulin intensified the effect of insulin. The hypoglycaemic effect of cerebrocrast primarily can be explained by its immunomodulative properties. Moreover, cerebrocrast can act through extrapancreatic mechanisms that favour the expression of glucose transporters, de novo insulin receptors formation in several cell membranes as well as glucose uptake.     

The effect of high-amylose cornstarch on lipid metabolism in OVX rats is affected by fructose feeding

We examined whether the effects of high-amylose cornstarch (HACS) on lipid metabolism in ovariectomized (OVX) rats were affected by high-fructose feeding. Sucrose (482 g/kg diet) was used as fructose source. OVX rats were fed one of the following four diets for 21 days: a sucrose-based or cornstarch-based cholesterol-free diet with or without HACS (150 g/kg diet). Body weight and food intake were increased by sucrose. Plasma total cholesterol and low-density lipoprotein cholesterol concentrations were increased by sucrose and decreased by HACS in cornstarch-fed rats, but not in sucrose-fed rats. Liver total lipids and concentrations of plasma and liver triacylglycerol (TAG) were increased by sucrose, whereas plasma TAG concentration was decreased by HACS, in sucrose-fed rats. However, liver cholesterol concentration was not affected by diet. The amount of cholesterol in small-intestinal contents was increased in sucrose-fed rats, but not in cornstarch-fed rats, but that of bile acids was not affected by diet. Fecal excretions of bile acids and neutral sterols were increased by HACS. The level of sterol-regulatory element-binding protein-1c mRNA was increased by sucrose and decreased by HACS in sucrose-fed rats, but not in cornstarch-fed rats. The level of farnesoid X receptor mRNA was decreased by sucrose and increased by HACS in cornstarch-fed rats, but not in sucrose-fed rats, as was the level of cholesterol 7α-hydroxylase mRNA. These results show that the effect of HACS on hyperlipidemia induced by ovarian hormone deficiency would be affected by the consumption of fructose-rich sweeteners such as sucrose and high-fructose syrup.     

Plasma Insulin in Response to Enterostatin and Effect of Adrenalectomy in Rats

Enterostatin has previously been reported to alter serum insulin and corticosterone levels after central administration of the peptide. The purpose of the present study was to investigate the effect of peripheral administration of enterostatin on insulin and corticosterone levels as well as the response of plasma insulin to enterostatin administration in adrena-lectomized rats. Female Sprague-Dawley rats were given a bolus injection intravenously with enterostatin alone or together with glucose. Enterostatin increased basal plasma levels of insulin, but significantly inhibited the increase in plasma insulin stimulated by glucose. Plasma corticosterone levels were not altered after a single intravenous injection of enterostatin. In rats infused chronically with enterostatin, plasma insulin levels were significantly reduced and plasma corticosterone levels were increased. The daily food intake was lower in these rats, but there was no effect on body weight. After adrenalectomy, the responsiveness of plasma insulin to enterostatin infusion was completely abolished. Furthermore, adrenalectomy itself reduced basal plasma levels of insulin and increased plasma levels of endogenous enterostatin. These results suggest that peripheral enterostatin administration produces a similar effect as central infusion of the peptide, and that the glucocorticoid hormones are involved in the regulation of plasma insulin by enterostatin.     

A comparative study of several serotonin receptor antagonists on basal and stimulus induced release of insulin and glucagon in the intact rat.

Several commonly used serotonin receptor antagonists were studied for their ability to influence basal plasma insulin and glucagon (using 30K antibody) levels as well as the response of these hormones to a glucose or arginine challenge administered systematically to overnight fasted rats. Cyproheptadine, in contrast to other antagonists employed, induced large increases of insulin, glucagon and glucose, although this hyperinsulinemia was of a smaller magnitude when compared with hormone levels observed during an equivalent hyperglycemia resulting from glucose administration. The pancreatic response to a glucose load (increased insulin and decreased glucagon release) and an arginine load (increased insulin and glucagon release) were prevented by cyproheptadine pretreatment. Basal insulin levels were bot consistently altered by methysergide or cinanserin and were slightly elevated by metergoline. Basal glucagon levels were unaffected by these drugs. These three agents potentiated the insulinotropic effect of an arginine load whereas only metergoline exerted a similar effect on the response to glucose loading. Glucagon release in response to these stimuli was not significantly altered by drug pretreatment.     

The effect of magnesium deficiency on glucose stimulated insulin secretion in rats

Weanling Sherman rats were pair-fed for 8 days on a control or a magnesium deficient diet containing 70.5% sucrose. After a 12-hour fast, the rats were injected intraperitoneally with glucose (250 mg/100 g body weight) and arterial blood was drawn at 0, 15, 30, 60, 90 minutes after injection. Before glucose loading, in magnesium deficient rats, plasma magnesium levels were significantly increased. The plasma triglyceride concentration was significantly higher in magnesium deficient rats compared to controls. After glucose loading, in the control group, the plasma insulin concentrations increased to 67.9 +/- 5.8 microU/ml at 15 minutes and returned to pretreatment levels by 30 minutes; in the magnesium-deficient rats, the plasma insulin levels were significantly lower at 15 minutes 32.9 +/- 5.6 microU/ml (P less than 0.01) and returned more slowly to the pre-challenge level. No significant differences were observed in plasma glucose levels between the two groups of rats.     

Effects of age and anesthetic on plasma glucose and insulin levels and insulin sensitivity in spontaneously hypertensive and Wistar rats

We examined the effects of anesthetic, age, and strain on oral glucose tolerance tests (OGTT, 1 g/kg body weight) and intraperitoneal glucose tolerance tests (IPGTT, 2 g/kg body weight) in spontaneously hypertensive (SH) and Wistar rats. Pentobarbital anesthesia caused an elevation in basal glucose and insulin levels in Wistar rats at 9 and 16 weeks of age and in SH rats at 9 weeks. Anesthesia increased the insulin output during an OGTT in both strains of rats while glucose was unchanged. Anesthesia reduced the insulin sensitivity index calculated from the OGTT but not from the IPGTT data. The age of the rats (9-11 vs. 16-18 weeks) had no effect on the basal glucose or insulin levels, but older Wistar rats had a greater insulin output following oral glucose and older SH rats had a greater insulin output following intraperitoneal glucose. On the basis of the insulin sensitivity index, SH rats were clearly more insulin resistant than age-matched Wistar rats. The SH rats also had higher basal insulin levels, as well as higher insulin output, following both glucose challenges. In summary, SH rats are more insulin resistant than Wistar rats, and anesthesia, which elevated basal glucose and insulin levels and increased the insulin output in response to a glucose challenge, may increase insulin resistance.     

Effect of High Sucrose Feeding on Fat Accumulation in the Male Wistar Rat

High sucrose intake is generally thought to be a risk factor for obesity and insulin resistance. We examined the effects of feeding sucrose on fat accumulation and insulin release in male rats. Six-week-old male Wistar rats were maintained on a high sucrose diet for 4 or 12 weeks. Control rats were fed a diet based on starch. No significant difference in daily caloric intake or weight gain existed between the two dietary groups. There was no difference between the two dietary groups in the gain of abdominal subcutaneous fat (SC) at 4-week. In contrast, rats fed the high sucrose diet had significantly more mesenteric fat (MES) than controls (p<0.01). At 12 weeks, rats fed the high sucrose diet had significantly more SC and MES than controls (SC:p<0.05, MES:p<0.01). Basal immunoreactive insulin (IRI) concentrations in the portal vein (PV) of rats fed the high sucrose diet was significantly higher compared to those of controls (4 wk: p<0.05, 12 wk: p<0.05). No difference between the two dietary groups in basal IRI concentrations in the inferior vena cava (TVC) existed at 4 weeks; whereas at 12 weeks, the basal IRI concentrations in the IV C in rats fed the high sucrose diet were significantly higher than in controls (p<0.05). The mesenteric and subcutaneous fat accumulations were closely related to hyperinsulinemia in the portal vein and inferior vena cava, respectively. Twelve weeks of high sucrose feeding caused accumulation of abdominal adipose tissue with marked hyperinsulinemia and hyperlipidemia. Our study is the first to demonstrate that abdominal fat induced by high sucrose intake in male rats is accompanied by an abnormal metabolic state similar to an insulin-resistant state.     

Effects of hypophysectomy and acute growth hormone treatment upon glucose metabolism in adipose tissues and isolated adipocytes of rats.

Glucose oxidation and incorporation into lipid were measured in epididymal adipose tissues and isolated adipose cells of normal and hypophysectomized rats in an effort to determine whether the acute hypoglycemic effect of a systemic growth hormone (GH) injection was related to alterations in the glucose metabolism of adipose tissue. The rats were fed rat chow or a high sucrose diet and received 100 mug GH intraperitoneally 30 minutes or three and one-half hours before sacrifice. Hypophysectomized rats showed a lower plasma glucose as compared with normal rats on both diets. Thirty minutes after a GH injection there was a further decrease of the plasma glucose which, however, was not present in those rats receiving GH three and one-half hours before sacrifice. Adipose tissues from hypophysectomized rats fed the high sucrose diet showed a blunted insulin sensitivity as compared with normal rats on a similar diet. The insulin sensitivity of these tissues was further decreased 30 minutes after a GH injection. Basal glucose metabolism of isolated adipocytes from hypophysectomized rats, as compared with normal rats, was depressed if they were fed rat chow, was at normal levels if they were fed the high sucrose diet and was increased if they were fed the sucrose diet and received triiodothyronine and cortisone supplements. No manipulations of diet or hormonal treatments made the isolated adipocyte from hypophysectomized rats sensitive to insulin either 30 minutes or three and one-half hours after a GH injection. Since basal glucose utilization is not enhanced by GH injection and both the blunted insulin sensitivity of adipose tissue and the absent insulin sensitivity of adipopocytes would be expected to produce hyperglycemia rather than hypoglycemia, it is concluded that immediate systemic effects of a GH injection on carbohydrate metabolism are not related to changes in glucose metabolism of the peripheral adipose tissues.     

Inhibited insulin secretion by recombinant human interleukin-1 beta in adrenalectomized rats: involvement of prostaglandin

An involvement of prostaglandin synthesis in reduced insulin secretion by interleukin-1 was investigated in adrenalectomized (ADX) rats. The recombinant human interleukin-1 beta (IL-1) significantly reduced insulin secretion in ADX rats 2 and 4 hr after the injection, although IL-1 stimulated insulin secretion in intact rats. In ADX rat, IL-1 showed dose-dependent inhibition of pancreatic insulin secretion. In addition, insulin response to intravenous glucose loading was also attenuated in ADX rats with pretreatment by IL-1. At 4 hours after injection, ibuprofen (IBP; 0.5-50.0 mg/kg, ip), selective cyclooxygenase blocker, attenuated insulin inhibition by IL-1 in a dose-dependent manner. These data suggest that IL-1 may suppress in vivo insulin release at least in part through the mediation of prostaglandin synthesis in the absence of adrenal glands.     

Secretion of glucagon and insulin in hypophysectomized rats: effect of tolbutamide.

Normal and hypophysectomized (hypox) rats, fed ad libitum, received intraperitoneal injections of tolbutamide (75 mg/kg/day) or of saline for 6 weeks. 24 h after the last injection, blood samples were taken for glucose, insulin and glucagon determinations. In normal rats, tolbutamide treatment did not alter serum glucose, insulin and glucagon, although it suppressed the secretion of insulin and glucagon by the pancreatic islets. In hypox rats, tolbutamide decreased serum glucose and insulin, elevated serum glucagon and stimulated the secretion of glucagon, but not that of insulin by the pancreatic islets. In addition, tolbutamide treatment increased the glucagon response to arginine in normal, but not in hypox rats. The serum glucose response to arginine was decreased by tolbutamide treatment and by hypophysectomy and, thus, appeared independent of the glucagon rise or preexisting glucagon level. We conclude that tolbutamide treatment decreased the secretion of glucagon and insulin in normal rats and stimulated that of glucagon in hypox rats, perhaps because of the low levels of insulin in the serum and in the pancreas of the latter. Our results are compatible with the hypothesis that the pancreatic action of tolbutamide is influenced by the pituitary.     

Insulin and C-peptide secretion in non-obese patients with polycystic ovarian disease

Plasma glucose, immunoreactive insulin (IRI) and C-peptide responses during an oral glucose tolerance test (oGTT) were assessed in 11 non-obese patients with polycystic ovarian disease (PCOD) and 11 reference subjects matched for age, height and weight. Also, 6 patients with PCOD and 6 normal women were subjected to intravenous glucose tolerance testing (ivGTT) On oGTT, all subjects exhibited normal glucose tolerance; however, PCOD patients had significantly higher mean plasma glucose levels at 30, 60, 90 and 120 min and higher mean incremental glucose areas. In addition the patients with polycystic ovaries showed higher mean basal IRI and C-peptide levels, higher mean glucose stimulated IRI and C-peptide levels and higher mean incremental IRI and C-peptide values. The molar ratios of C-peptide/IRI were significantly lower in the PCOD group at all time intervals after glucose stimulation when compared to the normal women. During ivGTT, there were significantly higher mean glucose levels at 5, 40, 50 and 60 min in the PCOD group when compared to the reference group. The IRI response to intravenous glucose in the PCOD women was similar to the reference group. The findings on oGTT suggest that non-obese patients with PCOD have increased pancreatic IRI secretion as well as impaired hepatic extraction of the hormone.     

Effects of electric stress on glucose metabolism, glucose-stimulated cyclic adenosine 3',5'-monophosphate accumulation and 45 Ca++ efflux in isolated pancreatic islets from rats fed with a high fat diet.

The effects of the electric stress on glucose oxidation, cyclic adenosine 3', 5'-monophosphate (AMP) accumulation and 45Ca++ efflux in response to glucose were studied in pancreatic islets isolated from rats fed on a control (C) or a high fat diet (F) for 12 weeks. The half of rats on each diet were subjected to electrical shocks in the random time schedule for 1 hr per day for the last 3 weeks of the feeding period (group C-S and F-S). The remaining rats were not given any shocks (group C-NS and F-NS). The rats in F-S group had the high levels of plasma epinephrine, dopamine and blood glucose. The basal content of cyclic AMP after 20 min of incubation with 2.8 mM glucose was decreased in islets from F-S group without affecting insulin release. After 20 min of incubation with 25 mM glucose, the cyclic AMP content in islets from F-S group, which was identical with that in F-NS group, was only 50% of that in C-S group. Insulin release in response to high glucose was significantly inhibited in islets from F-S group. In spite of a remarkable increase of cyclic AMP content in islets from C-S group, insulin release did not differ from that in C-NS group. Glucose (16.7 mM)-stimulated 45Ca++ efflux from the perfused islets was greatly inhibited by the high fat diet rather than by stress. The rate of glucose oxidation with 16.7 mM glucose was decreased in islets from F-S group. It is suggested that the decreased insulin release in response to glucose provoked by the combined effects of the feeding of a high fat diet and electric stress may be mediated by changes of the adenylate cyclase-cyclic AMP system on the plasma membrane of the B-cell or be related to changes in glucose metabolism in islets.