Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neuropeptide galanin is known to inhibit insulin secretion in a variety of species. However, controversies exist regarding its action on insulin secretion in the perfused pig pancreas, since both inhibitory and stimulatory effects have been described. We therefore perfused the isolated porcine pancreatico-duodenal block with galanin (100 nmol/l) in the presence of 5 or 15 mmol/l glucose or with 5 mmol/l glucose and 10 mumol/l tolbutamide. We found that at this dose level, galanin did not affect insulin secretion stimulated by glucose alone. In contrast, galanin clearly suppressed tolbutamide-stimulated insulin secretion. Hence, we conclude that galanin has a weak influence on insulin secretion in the pig pancreas, being unable to inhibit glucose-stimulated insulin secretion at the dose level of 100 nmol/l. However, when active, galanin clearly inhibits insulin secretion also in the pig pancreas.
Diabetes Res 1992 Feb
PMID:Galanin inhibits tolbutamide-stimulated insulin secretion in the perfused pig pancreas. 128 31

The changes in plasma gastrin-releasing peptide (GRP), arginine vasopressin (AVP), neuropeptide Y (NPY), corticotropin releasing hormone (CRH), galanin, ACTH, cortisol, delta sleep-inducing peptide (DSIP), adrenaline, noradrenaline and pancreatic polypeptide (PP) were measured after 5 and 15 minutes of acute insulin-induced moderate hypoglycaemia (2.0 mmol/l) in 10 patients with Type 1 diabetes mellitus with no autonomic neuropathy and in 10 healthy subjects. Plasma catecholamine and PP levels rose in both groups in response to hypoglycemia and the secretory response of ACTH was lower in the diabetic subjects (p < 0.01). GRP concentrations increased during hypoglycaemia (p < 0.01) while a reduction in AVP occurred at the start of hypoglycaemia (p < 0.001). The plasma AVP concentrations were higher in the diabetic group compared with those in the normal group (p < 0.05). The NPY concentrations were higher in the normal subjects (p < 0.05) but no change in the mean level occurred in either group during hypoglycaemia. No group differences or changes in mean plasma concentrations were found for galanin, DSIP and CRH. These observations support the view that regulatory peptides, if involved in glucose homeostasis, may rather have a modulatory effect than a direct action in restoring normoglycaemia.
Diabetes Res 1992
PMID:The response of regulatory peptides to moderate hypoglycaemia of short duration in type 1 (insulin-dependent) diabetes mellitus and in normal man. 128 60

Human progalanin cDNA was cloned with polymerase chain reaction techniques. The cDNA sequence predicts that the human form of galanin has a substitution of the glycine residue found at position 30 in other species and thus is likely to retain this residue during posttranslational processing and not be amidated at the COOH terminus. Furthermore, the cDNA sequence predicts three additional amino acid substitutions compared with known galanins. Human galanin was synthesized, and its bioactivity was compared with porcine and rat galanin based on inhibition of insulin release from a glucose-responsive rat insulinoma (RIN) cell line. Human galanin inhibited glucose-stimulated insulin secretion in a dose-dependent manner in RIN cells. Human, porcine, and rat galanin exhibited similar activity with ED50 less than 1 nM.
Diabetes 1992 Jan
PMID:Sequence of human galanin and its inhibition of glucose-stimulated insulin secretion from RIN cells. 137 Jan 55

Treatment of segments of ileum from 8-week streptozotocin-induced diabetic rats with phorbol 12,13-dibutyrate (PDBu) in vitro resulted in restoration of the diabetes-induced changes in the expression of enteric VIP- and galanin-like immunoreactive nerve fibres. The increase in fluorescence intensity and density of VIP- and galanin-like immunoreactivity observed in 8-week streptozotocin-treated rats was reduced to a near normal level after 40 min incubation of diabetic tissues in Krebs solution containing PDBu (100 nM). The tissue content of VIP was also affected (control = 2.1 +/- 0.31 pmol/cm; diabetic = 4.6 +/- 0.48 pmol/cm; diabetic + PDBu = 2.9 +/- 0.91 pmol/cm) after incubation with PDBu. The significance of these findings in relation to the possible role of protein kinase C in the regulation of expression and/or storage of these enteric neuropeptides in normal and diabetic states is discussed.
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PMID:Restoration of diabetes-induced changes in enteric nerves by phorbol 12,13-dibutyrate. 137 84

Plasma neuropeptide Y (NPY), plasma galanin and plasma catecholamines were determined before and during an ergometer exercise test in 11 type 1 diabetic patients (age 19-36 years, mean 30; duration of diabetes 2-18 years, mean 9) with autonomic dysfunction and in 13 age-matched healthy controls (age 24-36 years, mean 29). Before exercise, plasma NPY (100 +/- 6 pmol/l vs 144 +/- 7 pmol/l; P less than 0.001) and plasma galanin (54 +/- 3 pmol/l vs 77 +/- 5 pmol/l; P less than 0.005) were significantly lower in patients than in controls. During exercise, plasma NPY, plasma adrenaline, and plasma noradrenaline increased in patients and controls while galanin only increased in patients. Since there was a direct correlation between plasma NPY before exercise and the increment (delta 80%) in noradrenaline during exercise (r = 0.54; P less than 0.01), it is suggested that plasma NPY determined in the basal situation may be a useful marker of sympathetic nerve failure in diabetic patients.
Diabetes Res Clin Pract 1992 Mar
PMID:Plasma neuropeptide Y (NPY) and galanin before and during exercise in type 1 diabetic patients with autonomic dysfunction. 137 11

Neuropeptide Y (NPY) is a powerful appetite stimulant, and hypothalamic concentrations rise after food deprivation and in experimental diabetes. Serotonergic drugs such as dexfenfluramine are inhibitors of feeding. We measured hyothalamic NPY and NPY mRNA, along with galanin, neurotensin, and somatostatin in chow-fed rats and in rats with dietary obesity, and examined the effect of dexfenfluramine on these peptides in this model. Sixty-five rats were fed a palatable diet (condensed milk, sucrose and chow) for 6 weeks, which produced significant weight gain compared to twenty fed standard chow (145.1 +/- 2.3 g vs. 113.4 +/- 3.2 g, p less than 0.001). Groups of animals were treated for 7 days or 28 days with dexfenfluramine (1.8 mg/kg/day) or saline intraperitoneally via miniosmotic pumps. Hypothalami were dissected into medial and lateral blocks, and NPY, galanin, neurotensin, and somatostatin were measured by radioimmunoassay. Neuropeptide Y mRNA was measured by Northern blotting. Hypothalamic NPY was significantly higher in the palatable diet group compared to chow-fed controls (medial hypothalamus: 86.6 +/- 7.6 vs. 65.7 +/- 4.0 pmol/g tissue, p less than 0.02, lateral hypothalamus 71.2 +/- 6.6 vs. 53.1 +/- 3.6 pmol/g tissue, p less than 0.05), but NPY mRNA was unchanged. Although dexfenfluramine was effective at reducing weight gain in the animals fed the palatable diet, this did not result in any changes in the hypothalamic neuropeptides measured. Neuropeptide Y may be of importance in diet-induced obesity but the weight loss produced by dexfenfluramine in such animals is not mediated by changes in hypothalamic NPY.
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PMID:Dexfenfluramine treatment and hypothalamic neuropeptides in diet-induced obesity in rats. 138 31

The nature of the primary genetic defects in ob/ob and db/db mice are unknown. Both the obese (ob) and diabetes (db) mutations produce similar, multicomponent obese-hyperinsulinemic syndromes when maintained in the same strain of mouse. In an attempt to find differences between these mutations in neuroendocrine function affecting the islets of Langerhans or the pituitary, tissue content of four neuropeptides that are known to be capable of influencing the rate of insulin secretion was examined in obese (ob/ob) and diabetes (db/db) mice. In the first study, C57BL/6Job/ob and control males were studied at 3, 4, and 11 weeks of age. In the second study, db/db mice of both sexes and two inbred strains (C57BL/6J and C57BL/KsJ), which differ markedly in the severity of expression of the diabetes phenotype, were studied at 3 weeks of age, before the development of hyperglycemia and secondary consequences thereof. Immunoreactive peptides were measured in acetic acid extracts of pancreas and pituitary. No differences between male ob/ob and db/db mice of the C57BL/6J strain were found. Marked sex differences in lean control mice were found at 3 weeks of age in pancreatic Met-enkephalin-LI and galanin-LI (with two- to threefold higher content in males). Low pancreatic content (50% to 70% lower than in control mice) of galanin-LI, Met-enkephalin-LI and Leu-enkephalin-LI was associated with hyperinsulinemia in male B6 ob/ob and db/db mice at 3 weeks of age, though not in B6 db/db females and not in BKs db/db mice of either sex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuropeptide content in pancreas and pituitary of obese and diabetes mutant mice: strain and sex differences. 169 31

Results of studies on the effects of exogenous galanin on islet cell secretion are controversial. Until recently, only pig galanin has been available, and structural dissimilarities among the galanin molecules of different species might have contributed to discrepancies among the study results. Thus, we investigated the influence of synthetic rat galanin (50 nM) on unstimulated insulin, glucagon, and somatostatin release and on the responses of these hormones to arginine (10 mM), glucose (16.6 mM), and vasoactive intestinal polypeptide (VIP; 1 nM) in a homologous animal model, the perfused rat pancreas. In addition, the effect of an equimolar concentration of pig galanin on arginine-induced islet cell secretion was examined. Infusion of rat galanin reduced unstimulated insulin release (approximately 60%, P less than 0.01) and the insulin responses to arginine (approximately 30%, P less than 0.025), glucose (100%, P less than 0.01), and VIP (approximately 80%, P less than 0.025). Galanin also inhibited unstimulated somatostatin secretion (approximately 15%, P less than 0.05) and virtually abolished the somatostatin output evoked by arginine, glucose, and VIP. Conversely, rat galanin increased unstimulated glucagon output (approximately 20%, P less than 0.05), potentiated the glucagon response to arginine (approximately 50%, P less than 0.05) and VIP (approximately 90%, P less than 0.05), and counteracted the suppressor effect of glucose on alpha-cell secretion. Pig galanin inhibited the insulin output elicited by arginine (approximately 45%, P less than 0.05) but did not affect the somatostatin and glucagon responses to the aminogenic stimulus. In conclusion, the opposite effects of galanin on insulin and glucagon secretion favor the concept of galanin as a diabetogenic agent. Galanin also behaves as a potent inhibitor of somatostatin release. Finally, the importance of using homologous galanin to study the biological activity of this peptide must be emphasized.
Diabetes 1990 Aug
PMID:Inhibition of insulin and somatostatin secretion and stimulation of glucagon release by homologous galanin in perfused rat pancreas. 169 89

Galanin, an inhibitor of insulin secretion in pancreatic beta-cells, exerts its multiple effects through mechanisms that are sensitive to pertussis toxin (PTX). G proteins have been characterized in RINm5F cells. By ADP ribosylation and immunoblotting, the alpha-subunits of Gi1, Gi2, Gi3, and two forms of Go were identified, Gi alpha 2 being predominant. As expected from a G protein-linked receptor, GTP and its nonhydrolyzable analogue GTP-gamma-S decreased tracer galanin binding to cell membranes. This resulted from a change in receptor affinity without any modification in the number of sites. Selective antibodies against the COOH-terminal decapeptide of the alpha-subunits of the Gi and Go proteins were used to block G protein interaction before we studied galanin binding. Antibody AS, which selectively recognizes Gi alpha 1 and Gi alpha 2, decreased tracer galanin binding to membranes at concentrations where there were no effects of other antibodies specifically directed against Gi alpha 3 or G alpha o. These data suggest that Gi1 and/or Gi2 interact with the galanin receptor and probably mediate the effects of galanin in pancreatic beta-cells.
Diabetes 1991 Sep
PMID:Identification of G protein alpha-subunits in RINm5F cells and their selective interaction with galanin receptor. 171 2

Central and lateral hypothalamic concentrations of 9 regulatory peptides implicated in the control of feeding behaviour were measured in corpulent (cp/cp) JCR:LA-cp rats which develop spontaneous obesity, hyperinsulinaemia and hyperlipidaemia, and in lean (+/?) controls. In female cp/cp rats, central hypothalamic levels of neuropeptide Y (NPY), neurotensin, somatostatin and substance P were significantly lower (p less than 0.02) than in lean female controls. Following food restriction with a 16% reduction in body weight, these differences were apparently reversed and there were also significant rises in the lateral hypothalamic concentrations of neurotensin and of galanin. The other 4 peptides examined (bombesin, calcitonin gene-related peptide, neuromedin B and vasoactive intestinal peptide) did not differ significantly between cp/cp and lean females, either fed freely or food-restricted. Male cp/cp rats showed no significant differences from lean males in central or lateral hypothalamic concentrations of any of the 9 peptides. NPY and galanin are powerful and specific central appetite stimulants, whereas neurotensin, substance P and somatostatin inhibit feeding when injected centrally. Disturbances in these putative appetite-regulating peptides may be involved in the hyperphagia and other hypothalamic abnormalities in this spontaneous obesity syndrome. The apparent absence of differences between the male corpulent and lean groups may relate to sexual dimorphism of the syndrome, which is more marked in the females.
Diabetes Res 1990 Sep
PMID:Hypothalamic regulatory peptide disturbances in the spontaneously obese JCR: LA-corpulent rat. 172 Mar 64


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