Disturbances of basal and postprandial insulin secretion and clearance in obese patients with type 2 diabetes mellitus.

Hyperinsulinemia of nondiabetic overweight and obese subjects is associated with weight-dependent increased insulin secretion and decreased insulin clearance. The present analysis examines whether similar effects can be observed in overweight and obese patients with type 2 diabetes mellitus (DM2). Additionally basal and postprandial insulin secretion and clearance were analyzed in relation to duration of disease. In a random sample of 348 DM2 patients basal plasma insulin concentrations were significantly higher in most BMI groups compared to matched nondiabetic (ND) controls. The weight-dependent increase of basal insulin in DM2 was primarily the result of reduced clearance rather than augmented secretion. Postprandial insulin concentrations were lower in DM2 patients and did not show any BMI-related increase. The weight-dependent reduction of postprandial insulin clearance was absent in DM2. At the time of diagnosis basal insulin concentration was higher and secretion was comparable to ND subjects and this did not change with duration of diabetes. The early postprandial insulin response was still comparable between DM2 and ND subjects at the time of diagnosis but deteriorated with longer duration of disease. The later postprandial response at diagnosis (AUC 90-180) was characterized by significantly greater insulin secretion and concentration while later on the 3-fold higher secretion was paralleled by comparable peripheral plasma concentrations due to a significantly greater postprandial insulin clearance in DM2. In conclusion, the present data indicate that apart from disturbances of insulin secretion substantial changes of insulin clearance contribute to inadequate peripheral insulin concentrations in obese DM2 patients.

Effect of carbohydrate- and protein-rich meals on exercise-induced activation of lipolysis in obese subjects.

Exercise is an important part of obesity treatment concepts to support fat mobilisation from adipose tissue and also fat oxidation nolich is impaired in obese subjects. In normal weight subjects it is well known that stimulation of plasma insulin levels by a carbohydrate meal can inhibit lipolysis and subsequent fat oxidation. Since obese subjects frequently have elevated basal and postprandial insulin levels the effect of carbohydrate- and protein-rich test meals on exercise-induced activation of lipolysis is of special interest. Twenty obese subjects performed bicycle exercise for 30 min in the fasted state, 30 min after a carbohydrate-or a protein-rich meal, and 120 min after the carbohydrate meal (n=12), respectively, at low intensity. Activation of lipolysis was assessed by plasma glycerol levels. In addition, plasma insulin, glucose, and lactate concentrations were determined. In comparison to the fasted state, the carbohydrate meal suppressed activation of lipolysis. Following the protein meal, exercise led to an attenuated but significant increase of glycerol levels. A similar rise was observed when the carbohydrate meal was ingested 2 h prior to the exercise bout. To improve exercise-induced lipolysis and subsequent fat oxidation during low-intensity exercise obese subjects should not ingest carbohydrates immediately before exercise. Hunger sensations should be satisfied with protein-rich food. When carbohydrates are consumed 2 h prior to exercise its lipolytic effect is comparable to the protein meal. These data are useful in every day dietary counselling and might help to improve weight loss during obesity treatment.

Splanchnic somatostatin: a hormonal regulator of nutrient homeostasis.

Free (approximately 1600 daltons) somatostatin-like immunoreactivity was identified in arterial plasma of dogs that had received a test meal. Neutralization of circulating somatostatin while the dogs were consuming a fatty meal increased the plasma concentrations of triglycerides, gastrin, pancreatic polypeptide, and insulin after the meal. It is concluded that, in the dog, somatostatin is a true hormone that regulates the movement of nutrients from the gut to the internal environment.

Differential stimulatory effects of cannabinoids on VIP release and NO synthase activity in synaptosomal fractions from rat ileum.

Cannabinoid-1 (CB1) and CB2 receptors are present on neurons of the enteric nervous system. Our aim was to study whether cannabinoid receptor activation is involved in the regulation of VIP release and NO synthesis in isolated fractions of nerve terminals from rat ileum. VIP was measured by RIA and NO synthesis was analyzed using a L-[3H]arginine assay. Anandamide stimulated VIP release (basal: 245.9+/-12.4pg/mg, 10(-6)M: 307.6+/-11.7pg/mg, [n=6, P<0.05], 10(-7)M: 367.0+/-26.1pg/mg, [n=6, P<0.01]). The cannabinoid receptor agonist WIN 55,212-2 had similar effects (basal: 250.5+/-37.4pg/mg, 10(-6)M: 320.9+/-34.7pg/mg; [n=4, P<0.05]). The stimulatory effect of anandamide was blocked by the selective CB2 receptor antagonist, SR144528 (10(-7)M) (anandamide 10(-6)M: 307.6+/-11.7pg/mg; +SR144528: 249.0+/-26.3pg/mg, [n=6, P<0.05]), whereas the selective CB1 receptor antagonist SR141716 A had no effect. NO synthesis was stimulated by anandamide ([fmol/mg/min] basal: 0.08+/-0.01, 10(-6)M: 0.16+/-0.03; 10(-7)M: 0.13+/-0.02, n=4, P<0.05) and WIN 55,212-2 ([fmol/mg/min] basal: 0.05+/-0.01, 10(-6)M: 0.1+/-0.02, n=4, P<0.05). The anandamide reuptake inhibitor, AM 404 increased basal NOS activity ([fmol/mg/min] control: 0.1+/-0.04, 10(-6)M: 0.28+/-0.08, n=7, P<0.05). The stimulatory effect of anandamide on NO synthase was not antagonized by antagonists at the CB1, CB2 or TRPV1 receptor, respectively. In conclusion, in enteric nerves anandamide stimulates VIP release by activation of a CB2 receptor specific pathway, while the stimulation of NO production suggests the existence of an additional type of cannabinoid receptor in the enteric nervous system.

Pancreatic and gastric somatostatin release in response to intragastric and intraduodenal nutrients and HCl in the dog.

The effects of the instillation of glucose, fat, casein hydrolysate, and HCl into the gastrointestinal tract upon plasma levels of somatostatin-like immunoreactivity (SLI) in the venous effluent of the pancreas, fundus and antrum of the stomach, and in the inferior vena cava (IVC) were determined in normal laparotomized dogs. Fasting SLI levels in the effluent plasma from these sites were significantly greater than IVC levels. The intragastric administration of glucose elicited a prompt and significant rise in SLI levels in pancreatic, fundic and antral venous plasma, and in IVC plasma; intraduodenal glucose elicited smaller increments. After intragastric fat, a smaller, more gradual increase in the pancreatic and fundic effluents was observed, whereas the rise in antral SLI was minute, and IVC SLI did not rise significantly. Intraduodenal fat elicited a prompt increase in the pancreatic and antral vein SLI levels, and a small but significant increase in fundic and IVC plasma which suggests faster release of enteric factors that influence SLI secretion in the pancreas and antrum. Intragastric casein hydrolysate elicited a prompt increase in SLI in both the pancreatic and fundic veins, the latter being marked, but the antral SLI response was small; IVC SLI rose significantly within 15 min. Intragastric HCl provoked a prompt and marked rise in pancreaticoduodenal and antral vein SLI but no increase in fundic vein SLI; IVC SLI levels rose significantly within 20 min. Intraduodenal HCl elicited an even more prompt and marked pancreatic SLI response, and SLI rose significantly in both the fundic and antral venous effluents; IVC SLI also rose more promptly. In dogs with a gastric fistula that prevented intraduodenal entry of HCl, intragastric HCl elicited only a very small and transient rise in pancreaticoduodenal vein SLI, markedly stimulated the antral SLI response, but completely suppressed fundic venous SLI levels. The results indicate that all three nutrients stimulate SLI release from the pancreas and stomach. The greater SLI response to intragastric, as opposed to intraduodenal, glucose suggests that unidentified local factors are of importance. The responses to the intraduodenal instillation of HCl and fat suggest a role of enteric hormones in the release of SLI from the pancreas and fundus and antrum of the stomach. Additionally, there is evidence of direct effects of HCl upon gastric SLI release.

Properties of endogenous somatostatin-like immunoreactivity and synthetic somatostatin in dog plasma.

Somatostatin-like immunoreactivity (SLI) in the peripheral venous plasma of dogs and in their pancreatic and gastric venous effluents was characterized and compared with synthetic somatostatin. Both endogenuous plasma SLI and somatostatin added to plasma were eluted from Sephadex gels at pH 8.8 in the 150,000--200,000-mol wt region but at pH 2.5 both appeared in the 1,500--2,000-mol wt region. The SLI released from the isolated dog pancreas perfused with plasma-free buffer was eluted entirely as a 1,600-dalton polypeptide, but when the pancreas was perfused with plasma, SLI was eluted in the 150,000--200,000-mol wt zone. Affinity chromatography of plasma samples on immobilized antibodies directed against the central portion of the somatostatin molecule (residues 5--9 and 11) removed approximately equal to 90% of both endogenous SLI and somatostatin added to plasma, but neither was removed by affinity chromatography on antibodies directed against the NH2-terminal region of somatostatin (residues 1--4). The SLI from plasma and from pancreas perfusate isolated by affinity chromatography was identical in molecular size, charge, and immunometric properties to synthetic somatostatin. It is concluded that endogenous SLI is secreted by the pancreas and stomach in a form not distinguishable from synthetic somatostatin, but circulates in plasma bound to large molecular weight components; the NH2-terminal residues of somatostatin appear to be important in this binding.

Patient selection for surgical treatment of obesity.

A successful reduction of body weight in patients with morbid obesity (BMI >40 kg/m2) is difficult and in the majority of patients it is impossible with non-interventional treatment modalities. Surgical therapy is an efficient alternative for these patients. Potential surgical intervention, however, should be carefully evaluated during a six month preoperative treatment phase. During this time period indications and contraindications must be evaluated.

Modulatory glucose effect on bombesin-like immunoreactivity and gastrin secretion from isolated perfused rat stomach.

Previous studies have demonstrated mostly inhibitory effects of elevated plasma glucose levels on gastric exo- and endocrine as well as motor functions. Because increased plasma glucose levels reduce vagal activity via the central nervous system, it remains unclear if glucose exerts a direct effect on gastric functions. Therefore, our study was designed to determine the effect of acute changes in glucose concentrations on the release of gastrin and bombesin-like immunoreactivity (BLI) from the isolated perfused rat stomach. Acute elevations of perfusate glucose from 100 to 200 mg/dl or from 100 to 300 mg/dl augmented BLI secretion significantly without affecting gastrin release. During an acute decrease from 200 to 30 mg/dl, the secretion of both peptides remained unchanged. When acetylcholine was administered to stimulate BLI and gastrin secretion, the elevation of perfusate glucose to 200 mg/dl and the decrease to 30 mg/dl attenuated BLI secretion, whereas gastrin secretion remained unchanged compared with the control experiments at 100 mg/dl glucose. On the other hand, the perfusion of vasoactive intestinal peptide (VIP) and Leu-enkephalin had no effect on BLI and gastrin secretion during 100 mg/dl glucose perfusion, but both peptides elicited a significant stimulatory effect on BLI secretion during a perfusate glucose concentration of 200 mg/dl without affecting gastrin secretion. In conclusion, our study demonstrates first that an acute increase of glucose augments basal BLI secretion. Second, cholinergically induced BLI secretion is attenuated by hypo- and hyperglycemia. Third, hyperglycemia augments BLI secretion in response to the neuropeptides VIP and Leu-enkephalin. Fourth, basal and stimulated gastrin secretion remains unchanged during acute alterations of perfusate glucose levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulatory effect of glucose, amino acids, and secretin on CCK-8-induced somatostatin and pancreatic polypeptide release in dogs.

Protein- and fat-rich test meals elicit a strong stimulatory effect on postprandial somatostatin (SLI) and pancreatic polypeptide (PP) release, whereas carbohydrate-rich meals rather attenuate the response of both hormones. Since there is evidence that intestinal hormones might contribute to the postprandial SLI and PP response, it was the aim of the present study to determine in dogs the effect of low-dose cholecystokinin octapeptide (CCK-8) on basal hormone levels and also during a background infusion of amino acids or glucose. In a group of six conscious dogs, sulfated CCK-8 was infused intravenously (i.v.) via a hindleg vein at stepwise increasing infusion rates of 10, 30, and 50 pmol X kg-1 X h. The infusion of CCK was applied during a background infusion of saline (2 ml/min), glucose (0.2 g/min), or an amino acid mixture (8.5%, 2 ml/min). CCK-8 had no effect on plasma insulin and glucagon levels under all experimental conditions. Plasma SLI levels were significantly stimulated by all doses of CCK. This stimulatory effect was similar during background infusions of either saline, glucose, or amino acids, respectively. Pancreatic polypeptide (PP) levels rose 200-300 pg/ml during CCK plus saline. This was slightly attenuated by glucose. During CCK plus amino acids, the PP response was augmented to 600-800 pg/ml. Since secretin is also released after the ingestion of a meal and intraduodenal acidification is a potent stimulus not only of secretin but also of gastric and pancreatic SLI release, the effect of secretin was examined additionally.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin inhibits somatostatin-like immunoreactivity release stimulated by intragastric HCl.

To determine the effect of an increase in insulin levels within the range occurring under physiologic conditions on the protein- and acid-induced release of splanchnic somatostatin, insulin was infused in dogs for 1 h following the intragastric instillation of a neutral protein load (20% liver extract at pH 7), a weak stimulus of somatostatin-like immunoreactivity (SLI), and after an intragastric HCl, a strong stimulus of SLI release, instilled 30 min later. Insulin levels between 50 and 60 microunits/ml significantly reduced the rise in peripheral venous SLI levels elicited by the acid load from a mean integrated incremental value of 1705 +/- 182 pg/ml in controls to 840 +/- 312 in the insulin-infused group (P less than 0.05). Prevention of the insulin-induced hypoglycemia and the secondary rise in glucagon, a known stimulus of pancreatic somatostatin secretion, by means of a concomitant infusion of glucose, did not modify the reduction in acid-induced increase in plasma SLI concentration associated with hyperinsulinemia. Insulin-glucose infusion significantly lowered the SLI in the pancreaticoduodenal vein, and in the gastroepiploic vein draining the antrum (P less than 0.02; P less than 0.05), but not in the short gastric veins draining the fundus of the stomach in response to the acid load. It is concluded that physiologic elevation of insulin levels causes significantly reduced response of SLI to an intragastric acid load in dogs. This reduction is explained by a diminished increment of SLI in the venous effluent of the pancreas and the antrum.

Evidence for an effect of exorphins on plasma insulin and glucagon levels in dogs.

Recently, peptides with opioid-like activity have been demonstrated in peptic digests of dietary protein. The present study was designed to determine the effect of digested and undigested gluten on postprandial insulin and glucagon levels in conscious dogs. The intragastric instillation of digested gluten (25 g) elicited a more rapid and a significantly greater rise in postprandial peripheral vein insulin and glucagon levels compared with the effect of 25 g undigested gluten. The incremental insulin level was 104 +/- 20 microU/ml after digested gluten and only 58 +/- 7 microU/ml (P less than 0.01) after undigested gluten; the respective values for glucagon are 426 +/- 25 pg/ml versus 302 +/- 20 pg/ml (P less than 0.01). The intragastric administration of naloxone (4 mg), a specific opiate receptor antagonist, reduced the insulin response and augmented the glucagon response to the digested gluten test meal, whereas the response of both hormones to the undigested gluten meal was not affected by naloxone. Intravenously infused naloxone during the digested gluten meal did not influence insulin or glucagon levels. The present data suggest that in dogs the peptic digest of gluten contains an opioid-like material that stimulates postprandial insulin and glucagon release.

Effect of low-dose somatostatin infusion on pancreatic and gastric endocrine function in lean and obese nondiabetic human subjects.

The present study was designed to compare, in lean and obese nondiabetic subjects, basal and postprandial levels of peripheral venous plasma insulin, glucagon, gastrin, pancreatic polypeptide (PP), glucose, triglycerides, and somatostatin-like immunoreactivity (SLI) during the infusion of synthetic somatostatin-14 or saline. Thirty-five minutes before the ingestion of the test meal, an infusion of synthetic somatostatin-14 was started at a rate of 0.5 ng/kg X min and was increased to 1.0 ng/kg X min 30 min after consumption of the meal and lasted for another 90 min. During the infusion of saline, basal peripheral vein levels of insulin, gastrin, and triglycerides were elevated in obese subjects, whereas basal plasma SLI levels were significantly lower compared with the lean controls. Basal glucagon and PP levels were similar in both groups. After the ingestion of the meal, augmented concentrations of insulin and gastrin were observed in the obese subjects, whereas postprandial SLI and PP levels were reduced. Chromatography of fasting plasma revealed all measurable SLI to be confined to the void volume fractions of a Bio-Gel P-10 column. The rise in SLI after the meal was due to an increase of SLI co-eluting with somatostatin-28 and somatostatin-14. During the infusion of somatostatin, only basal insulin levels were significantly lower in the obese subjects, whereas no change of any basal hormone level was observed in the lean group. During the infusion of somatostatin, SLI levels were elevated by 20-30 pg/ml in both groups compared with the saline controls. During the infusion rate of 0.5 ng/kg X min, only postprandial PP levels were reduced significantly in the obese group, while all the other parameters were unaffected in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Pertussis toxin reverses prostaglandin E2- and somatostatin-induced inhibition of rat parietal cell H(+)-production.

In enzymatically dispersed enriched rat parietal cells we studied the effect of pertussis toxin on prostaglandin E2 (PGE2)- or somatostatin-induced inhibition of H(+)-production. Parietal cells were incubated in parallel in the absence (control cells) and presence of pertussis toxin (250 ng/ml; 4 h). [14C]Aminopyrine accumulation by both pertussis toxin-treated and control cells was used as an indirect measure of H(+)-production after stimulation with either histamine, forskolin or dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP) alone and in the presence of PGE2 (10(-9)-10(-7) M) or somatostatin (10(-9)-10(-6) M). PGE2 inhibited histamine- and forskolin-stimulated [14C]aminopyrine accumulation but failed to alter the response to dbcAMP. Somatostatin was less effective and less potent than PGE2 in inhibiting stimulation by histamine or forskolin and reduced the response to dbcAMP. Pertussis toxin completely reversed inhibition by both PGE2 and somatostatin on histamine- and forskolin-stimulated H(+)-production but failed to affect inhibition by somatostatin of the response to dbcAMP. After incubation of crude control cell membranes with [32P]NAD+, pertussis toxin catalysed the incorporation of [32P]adenosine diphosphate (ADP)-ribose into a membrane protein of molecular weight of 41,000, the known molecular weight of the inhibitory subunit of adenylate cyclase (Gi alpha). Pertussis toxin treatment of parietal cells prior to the preparation of crude membranes almost completely prevented subsequent pertussis toxin-catalysed [32P]ADP ribosylation of the 41,000 molecular weight protein.(ABSTRACT TRUNCATED AT 250 WORDS)

[Bariatric surgery. Patient selection and indication]. / Adipositaschirurgie: Patientenselektion und Indikationsstellung.

Successful reduction of body weight in patients with morbid obesity (BMI >40 kg/m(2)) is difficult and on a long-term basis nearly impossible with non-interventional treatment modalities. Surgical therapy is an efficient alternative for these patients. Potential surgical treatment should be carefully evaluated during a 6-month preoperative treatment phase during which indications and contraindications should be evaluated. Qualified postoperative care must be provided.

Effect of motilin on gastric emptying in patients with diabetic gastroparesis.

OBJECTIVES: Because disturbances of gastric emptying are a serious complication in insulin-dependent diabetic subjects with regard to the maintenance of good metabolic control, we wanted to assess the effectiveness of motilin as a potential treatment for gastric emptying disturbances. RESEARCH DESIGN AND METHODS: The intestinal hormone motilin has been shown to accelerate gastric emptying in healthy subjects. Therefore, we examined the effect of intravenous motilin on gastric emptying of a 99mTc colloid-labeled semisolid test meal in 9 insulin-dependent diabetic patients with diabetic gastroparesis. All patients had a significantly delayed gastric emptying rate compared with a group of 11 healthy control subjects. RESULTS: During the infusion of motilin, gastric emptying was accelerated, and it was no longer significantly different from control values. CONCLUSIONS: These data demonstrate that motilin and related compounds such as erythromycin derivatives could be useful for the treatment of disturbed gastric emptying in diabetic subjects.

Half-life of somatostatin-like immunoreactivity in canine plasma.

Previous estimates of the half-life of synthetic somatostatin have been based upon the disappearance rate of 125I-labeled Tyr1-somatostatin. In the present study, the half-life of infused synthetic somatostatin was determined by RIA and compared with the duration of its suppressive action upon plasma insulin and glucagon. After the end of a 2-h infusion of somatostatin (500 ng/min), the radioimmunologically measured half-life was 1.82 min. The reappearance half-times for insulin and glucagon were 1.4 and 6.7 min, respectively. These data show that calculations of the half-life of somatostatin-like immunoreactivity in plasma may differ from estimates based on the duration of its biological activities, which may differ from one another.

Free somatostatin in the circulation: amounts and molecular sizes of somatostatin-like immunoreactivity in portal, aortic, and vena caval plasma of fasting and meal-stimulated dogs.

Somatostatin-like immunoreactivity (SLI) of plasma from the portal vein, aorta, and inferior vena cava and of lymph from the thoracic duct of both fasted and meal-stimulated dogs was measured and characterized with respect to molecular size. Significant portal vein-arterial and arteriovenous SLI gradients were present in fasting dogs, and they increased sharply after the intragastric infusion of liver extract and HCl. Chromatography of fasting plasma at pH 7.4 revealed all measurable SLI to be confined to the void volume fractions of a Bio-Gel P-6 column, although, after a 7-fold concentration of fractions coeluting with somatostatin, approximately 1600-daltion SLI was detected in the portal venous plasma. The rise in SLI after a meal was due primarily to an increase of approximately 1600-dalton SLI; approximately 1600-dalton SLI was detectable in unconcentrated portal venous and aortic plasma and in the peripheral venous plasma concentrated 7-fold. SLI levels in lymph were similar to those of basal venous plasma and did not increase with a meal. This first demonstration at a physiological pH of a approximately 1600-dalton SLI in the arterial circulation suggests that a free, readily available form of endogenous somatostatin is present in the canine circulation and could be playing a hormonal role.

Properties of somatostatin-like immunoreactive polypeptides in the canine extrahypothalamic brain and stomach.

Polypeptides with somatostatin-like immunoreactivity (SLI) and approximate molecular weights of 12,000, 3,000, and 1,600 were isolated from acid extracts of the canine extrahypothalamic brain and stomach by affinity chromatography, ion exchange, gel filtration, and isoelectric focusing. The 12,000-dalton SLI was acidic, whereas the 3,000- and 1,600-dalton forms were basic molecules. All SLI fractions diluted proportionally in a RIA employing an antibody directed toward the central region of somatostatin. Like synthetic somatostatin, the 1,600-dalton SLI inhibited pentagastrin-stimulated gastric acid secretion in rats. Neither of the two larger forms of SLI were dissociated by 6 M guanidinium HCl. However, treatment with dithiothreitol, which reduces disulfide bonds, resulted in the conversion of a large portion of the 12,000-dalton SLI to the 1,600-dalton form. These data are compatible with a model of a 12,000-dalton SLI consisting of somatostatin bound to an acidic polypeptide by a peptide bond and a disulfide bond. Variations in the relative rates of hydrolysis of the peptide bonds and reduction of the disulfide bonds in different tissues may result in three forms of the 12,000-dalton polypeptide in which both bonds are intact or one of the two bonds is cleaved.

Origin of peripheral venous hypersomatostatinemia in alloxan-diabetic dogs.

Basal and postprandial somatostatin-like immunoreactivity (SLI) is elevated in the peripheral venous plasma of chronic alloxan-diabetic dogs. To determine if this hypersomatostatinemia was the consequence of increased somatostatin release from the pancreas, stomach, or both, plasma SLI was measured in the pancreaticoduodenal, antral, and fundic veins and in the inferior vena cava in response to stimulation by a gastric liver test meal, followed by an intragastric HCl load. Basal and postprandial inferior vena caval plasma SLI levels were significantly higher than the control level (P less than 0.05-0.001), confirming earlier findings. Basal pancreatic venous SLI was 780 +/- 45 pg/ml in the diabetic dogs and 493 +/- 65 pg/ml in the controls (P less than 0.02). In response to the liver meal at pH 7, the incremental pancreatic venous SLI level in the diabetic dogs was 1630 +/- 95 pg/ml, and after HCl it rose to 9479 +/- 384 pg/ml compared to 938 +/- 80 and 4677 +/- 192 pg/ml, respectively, in the controls (P less than 0.02 and P less than 0.005). However, antral and fundic venous SLI levels in the diabetic dogs did not differ from the controls in either basal or stimulated states. The present data demonstrate that the pancreas and not the stomach is the probable source of the peripheral hypersomatostatinemia of alloxan-diabetic dogs.

Morphine-induced hyperglycemia: role of insulin and glucagon.

An iv bolus injection of 0.5 mg/kg morphine, about twice the therapeutic dose, caused plasma glucose to rise more than 120 mg/dl in alloxan-diabetic conscious dogs but had little effect on conscious normal dogs. Plasma glucagon rose in the diabetic and nondiabetic groups by 30 +/- 10 and 100 +/- 29 pg/ml, respectively, but insulin levels increased significantly only in the nondiabetics. The hyperglycemic action on morphine may, at least in part, be the result of an increase in glucagon secretion without a sufficient accompanying release of insulin.