Effects of galanin on insulin and glucagon secretion in the rat

Galanin-like immunoreactivity has been visualized in nerve fibers in the islets of Langerhans, suggesting an involvement of galanin in the neural regulation of islet function. In this study, we investigated the effects of galanin on basal and stimulated insulin and glucagon secretion by infusing the peptide at three different dose rates in rats. We also studied the direct effect of galanin on insulin secretion from freshly isolated rat islets. At 320 pmol/kg/min, but not at 20 or 80 pmol/kg/min, galanin lowered basal plasma insulin levels. In contrast, basal plasma glucagon levels were lowered by galanin already at 20 and 80 pmol/kg/min. Furthermore, galanin inhibited both glucose- and arginine-induced insulin release at all three dose levels, whereas arginine-induced glucagon release was not affected by galanin. Glucose-stimulated insulin secretion from isolated rat islets was dose-dependently suppressed by galanin (10^-6-10^-8M). Therefore, it is concluded that galanin in rats inhibits insulin secretion, both in vivo and in vitro, and that at lower dose levels, the peptide also inhibits basal glucagon release.     

Smoking and coffee intake following alcohol withdrawal in alcoholic inpatients

The aim of this study was to assess alcoholic inpatients' smoking and coffee intake variation following withdrawal. Only moderate smokers (less than 30 cigarettes/day) showed a significant increase of cigarette consumption after alcohol withdrawal. However, their urinary cotinine level did not vary, suggesting a behavioral, and not biological, compensation through smoking following alcohol withdrawal. Heavy smokers (30 cigarettes/day or more) showed no significant clinical or biological variation of smoking behavior. Coffee consumption increased after alcohol withdrawal in all patients, irrespective of smoking habits.     

Validation in the sheep of an ultrasound velocity dilution technique for haemodialysis graft flow

BACKGROUND: A simple, rapid, inexpensive method for measuring the flow in a patient's vascular access would permit routine monitoring during haemodialysis, and hence provide information of access graft deterioration sufficiently early to increase the success of minimally invasive remedial procedures. This paper reports the validation of such a method in animals. METHODS: A PTFE graft was implanted in sheep between the carotid artery and the jugular vein. While the sheep was under general anaesthesia and on an haemodialysis circuit, ultrasound velocity in its blood was perturbed by the injection of a 5-10 ml bolus of isotonic NaCl. The pump tubing flow was measured by a transit-time blood flow meter. This flow was combined with the areas of perturbation generated by the injection before and after mixing in the access flow to estimate graft flow. The calculated graft flow was compared to flow measured directly by a transit-time probe on the same carotid artery. RESULTS: Over a 10-fold range, 120-1260 ml/min, graft flow measured by ultrasound velocity dilution agreed well with graft flow measured directly with a scatter of 76 ml/min about the regression line. CONCLUSION: Ultrasound velocity dilution provides a method for measuring flow in the graft accurate enough for clinical evaluation of patients on dialysis.      

Glycogen and glycogen-hydrolysing lysosomal enzyme activity in mouse liver: effects of fasting, adrenoceptor antagonism and insulin-induced hypoglycaemia

Whereas the phosphorolytic breakdown of liver glycogen is known to be of great physiological importance, the functional role of the hydrolytic glycogenolysis in the lysosomal system is less well understood. In the present study the effects of fasting, alpha- and beta-adrenoceptor antagonism and insulin-induced hypoglycaemia on liver lysosomal glycogen-hydrolysing enzyme activity were investigated in mice. In freely fed mice the glycogen-hydrolysing activity (acid amyloglucosidase) was only 50% of the maltose-hydrolysing activity (acid maltase). Starvation for 24 h reduced the acid amyloglucosidase activity by approximately 30% (P less than 0.001), whereas the activities of acid maltase, acid phosphatase and beta-glucuronidase appeared unaffected. N-acetyl-beta-D-glucosaminidase activity was moderately (20%; P less than 0.01) enhanced by fasting. Thus, liver lysosomal enzyme activities may change independently of each other during fasting. Further, during short-term hypoglycaemic conditions (45 min) induced by endogenous or exogenous insulin, the activity of liver acid amyloglucosidase was found to be moderately reduced (15-20%). Blockade of alpha- and beta-adrenoceptors by phentolamine and propranolol did not result in any apparent influence on acid amyloglucosidase activity except for the indirect effect exerted by the phentolamine-induced hypoglycaemia. A moderate negative correlation (r = -0.51; P less than 0.001) between total liver glycogen concentration and acid amyloglucosidase activity was observed in a series of 43 freely fed NMRI mice. Our data show that in mouse liver the acid maltase activity predominates over the acid amyloglucosidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuropeptide Y and calcitonin gene-related peptide: effects on glucagon and insulin secretion in the mouse

Neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) are both intrapancreatic neuropeptides that are known to inhibit stimulated insulin secretion. In the present study, we examined their influences on basal and stimulated glucagon and insulin secretion in the mouse. Either NPY or CGRP was injected intravenously at two dose levels (0.85 or 4.25 nmol/kg). When injected alone, neither of them did affect basal plasma glucagon levels but CGRP reduced basal plasma insulin levels. Glucagon secretion stimulated by the cholinergic agonist carbachol was modestly inhibited by NPY at 4.25 nmol/kg (P less than 0.01) but not affected by CGRP. In contrast, glucagon secretion stimulated by the beta 2-adrenoceptor agonist terbutaline was markedly inhibited by NPY already at the lower dose level (P less than 0.01) and potentiated by CGRP (P less than 0.01). Insulin secretion stimulated by carbachol was inhibited by CGRP (P less than 0.01) but not affected by NPY, whereas terbutaline-induced insulin secretion was inhibited by both NPY (P less than 0.05) and CGRP (P less than 0.01). We conclude that the two intrapancreatic neuropeptides NPY and CGRP have opposite actions on stimulated glucagon secretion in the mouse: NPY in an inhibitory and CGRP in a potentiatory direction. Both peptides, however, inhibit insulin secretion stimulated by terbutaline.     

The intestinal peptide PEC-60 inhibits insulin secretion in the mouse and the rat.

The newly discovered 60-amino-acid porcine intestinal peptide, PEC-60, shows a structural similarity to pancreatic secretory trypsin inhibitor. PEC-60 was recently demonstrated to inhibit glucose-stimulated insulin secretion from the perfused rat pancreas. We examined in this study whether the peptide affects basal and stimulated insulin secretion in vivo. Purified porcine PEC-60 was injected intravenously in mice at 1 or 8 nmol/kg alone or together with glucose (2.8 mmol/kg) or the cholinergic agonist carbachol (0.16 mumol/kg). PEC-60 was found to inhibit glucose- and carbachol-induced insulin secretion (p less than 0.01 and p less than 0.05, respectively) at 8 nmol/kg, whereas at 1 nmol/kg, the peptide had no effect. In contrast, basal plasma insulin levels were not affected by PEC-60. In a second experimental series, PEC-60 was infused intravenously in rats at 17 or 68 pmol/min alone or together with glucose (56 mumol/min). At 68 pmol/min (p less than 0.01), but not at 17 pmol/min, PEC-60 inhibited glucose-stimulated insulin secretion. The peptide had no influence on basal plasma insulin levels. It is concluded that the newly isolated intestinal peptide, PEC-60, inhibits stimulated insulin secretion under in vivo conditions both in the mouse and in the rat without affecting basal insulin secretion.     

Prevention of hyperglycemia improves the long-term result of islet transplantation in streptozotocin-diabetic rats.

We examined the hypothesis that prevention of hyperglycemia during the critical period immediately following islet transplantation will improve the outcome of the transplantation in streptozotocin-diabetic rats. Two days after intravenous injection of streptozotocin (70 mg/kg), 400 or 1,000 islets were transplanted into the left kidney subcapsular space. A group of rats transplanted with 400 islets was treated with insulin from 1 day before transplantation and for 7 days. Intravenous glucose infusion was performed at 10 days and 3 months after transplantation. In addition, at 3 months, the grafts were examined by light and electron microscopy. We found that rats transplanted with 400 islets without any concomitant insulin administration remained diabetic throughout the 3-month period and no plasma insulin response was induced by glucose infusion in these rats. In contrast, diabetic rats transplanted with 400 islets and treated with insulin for 7 days remained normoglycemic throughout the 3-month period, as did rats transplanted with 1,000 islets. Furthermore, these rats had normal glucose-stimulated insulin secretion both at 10 days and at 3 months after transplantation. Moreover, islet grafts from rats transplanted with 400 islets and administered insulin as well as from rats transplanted with 1,000 islets were morphologically normal, and following removal of the graft, hyperglycemia developed rapidly. In contrast, the islet grafts from rats transplanted with 400 islets without concomitant insulin administration had only few insulin cells. Thus, by preventing hyperglycemia at the time of islet transplantation, the long-term result of islet transplantation was improved. Therefore, the ambient glucose level initially following islet transplantation is critical for the long-term result.     

Reduced pancreatic content of the inhibitory neurotransmitter galanin in genetically obese, hyperinsulinemic mice.

Because abnormalities of the autonomic nervous system have been described in several animal models of obesity, and because galanin has been proposed to be a sympathetic neurotransmitter in the endocrine pancreas, we hypothesized that the hyperinsulinemia observed in genetically obese (ob/ob) mice may result either from defective ability of galanin to inhibit insulin release or from a reduced degree of pancreatic galaninergic innervation. To address these possibilities, we examined the effect of exogenous galanin on immunoreactive insulin (IRI) levels in ob/ob mice and compared the pancreatic content of galaninlike immunoreactivity (GLIR) in ob/ob mice with that in lean littermates. Intravenous administration of synthetic porcine galanin significantly reduced basal IRI levels in ob/ob mice, suggesting that a defect in galanin action is unlikely to account for the hyperinsulinemia in this model. In contrast, reduced pancreatic galaninergic innervation was supported by findings that pancreatic content of GLIR in ob/ob mice was less than 10% of that in age- and sex-matched lean littermates. The reduction of pancreatic GLIR in ob/ob mice appeared organ specific; no such reduction was observed in adrenal GLIR content when comparing obese and lean mice. In addition, the relationship between pancreatic GLIR content and plasma IRI levels was examined in groups of obese and lean mice. It was found in young females, young males, and older mice of mixed sex that there was a significant negative correlation between pancreatic GLIR and plasma IRI in lean mice, whereas no such correlation was observed in obese mice.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combination of ABO blood group incompatibility and glucose-6-phosphate dehydrogenase deficiency: effect on hemolysis and neonatal hyperbilirubinemia

The incidence (%) of hyperbilirubinemia (serum bilirubin ≥257 μmol/l) was similar in neonates with a combination of ABO incompatibility and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (45%), with ABO incompatibility (54%) or G-6-PD deficiency (37%), alone (ns). Carboxyhemoglobin values, corrected for inspired CO, were similarly elevated in all three groups (0.87 ± 0.32%, 0.82 ± 0.29%, 0.76 ± 0.18%, respectively, ns), but correlated with bilirubin only in those with ABO incompatibility alone. ABO-incompatible/G-6-PD-deficient neonates, compared with those with either condition alone, are not at increased risk for hemolysis or hyperbilirubinemia.