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 effect of calcitonin gene-related peptide (CGRP) on glucose metabolism was investigated in conscious and unrestrained rats in vivo. Intravenous injection of rat CGRP (5.67 and 0.567 nmol/kg) caused a significant, dose-dependent increase in plasma glucose concentration and a simultaneous dose-dependent increase in plasma insulin level. In contrast, plasma glucagon level was not changed. On the other hand, intravenous infusion of CGRP (46.6 pmol.kg-1.min-1) decreased tolerance to intragastric administration of glucose (IGGTT). Plasma insulin response to IGGTT, however, was not affected by CGRP infusion. Moreover, although intravenous injection of CGRP (5.67 nmol/kg) elicited a significant increase in plasma epinephrine and norepinephrine concentrations, concomitant administration of epinephrine and norepinephrine, inducing a more prominent rise in plasma catecholamines than those induced by CGRP, affected neither plasma glucose nor insulin levels. Finally, plasma insulin levels obtained by simulating CGRP-induced changes in plasma glucose or glucose plus catecholamine levels by infusion of glucose or glucose plus catecholamines were not different from those induced by CGRP injection. These results suggest that CGRP has a hyperglycemic action that is not mediated by sympathetic outflow in conscious rats, and inhibition of insulin secretion, if any, does not play a major role in this hyperglycemic action of CGRP. We have demonstrated specific CGRP receptors linked to adenylate cyclase activation in rat liver plasma membranes; this hyperglycemic effect of CGRP in vivo may be partly due to its direct action on the liver.
Diabetes 1990 Feb
PMID:Calcitonin gene-related peptide and induction of hyperglycemia in conscious rats in vivo. 222 23

During hyperinsulinemic glucose-clamp studies, intravenous infusion of calcitonin gene-related peptide (CGRP) in rats antagonized the ability of insulin to stimulate peripheral glucose disposal by 52% (196 +/- 7.2 vs. 105 +/- 10.5 mumol.kg-1.min-1, P less than 0.05) and to inhibit hepatic glucose output by 54% (P less than 0.01). CGRP also inhibited the in vitro effects of insulin to stimulate hexose uptake in cultured BC3H1 myocytes at all insulin concentrations studied. Amylin is a peptide isolated from amyloid deposits in pancreatic islets of type II (non-insulin-dependent) diabetic subjects, is present in normal beta-cells, and bears a striking homology to CGRP. When synthetic human amylin was infused during clamp studies, it inhibited the ability of insulin to stimulate glucose disposal by 56% (96.9 +/- 9.4 vs. 42.4 +/- 5.0 mumol.kg-1.min-1, P less than 0.05) and to suppress hepatic glucose output by 64%. Therefore, amylin and CGRP can cause insulin resistance in vivo and may be implicated in insulin-resistant states such as type II diabetes mellitus.
Diabetes 1990 Feb
PMID:Induction of insulin resistance in vivo by amylin and calcitonin gene-related peptide. 222 35

Amylin amide, a 37-amino acid peptide that is a major component of amyloid deposits in the diabetic pancreas, possesses vasodilator activity. Human synthetic amylin amide (30 to 300 pmol/site) stimulated a dose-dependent increase in blood flow after intradermal injection in rabbit skin. Amylin amide was 100 times less active than the structurally related potent vasodilator neuropeptide calcitonin gene-related peptide. Amylin amide did not induce edema formation; however, as a consequence of its vasodilator activity, amylin amide potentiated edema formation induced in rabbit skin by bradykinin. The intravenous injection of amylin amide (10 nmol) caused a systemic drop in blood pressure. This study demonstrates that amylin amide elicits vasodilator responses in vivo. It is possible that the release of amylin amide from the pancreas in type II diabetes could lead to changes in vascular tone.
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PMID:The demonstration of vasodilator activity of pancreatic amylin amide in the rabbit. 231 20

Pancreatic islet amyloid deposits were found in 22 of 24 type-2 diabetic subjects (aged 48-68 years) and were not present in 10 age-matched controls. A novel peptide, 37 aminoacids long, termed diabetes-associated peptide (DAP), has been identified in amyloid-containing pancreatic extracts from 3 type-2 diabetic patients but not in extracts from 6 non-diabetic subjects. DAP has major homology with calcitonin-gene related peptide (CGRP) and the islet amyloid of all 22 diabetics showed CGRP immunoreactivity. The immunoreactivity was inhibited by preabsorption of three different CGRP antisera either with CGRP carboxyterminal peptide 28-37 or with extracted DAP. Both diabetic and non-diabetic subjects had CGRP/DAP immunoreactivity in islet B-cells. Electron microscopy of islets containing amyloid indicated fibrillar amyloid between the endocrine cells and capillaries, usually penetrating into deep invaginations of the plasma membrane of the B-cells. These results suggest that islet amyloid contains DAP, which may originate from B-cells. Accumulation of amyloid in islets is likely to impair islet function and may be a causal factor in the development of type-2 diabetes.
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PMID:Islet amyloid formed from diabetes-associated peptide may be pathogenic in type-2 diabetes. 244 Dec 14

The simultaneous release of endogenous acetylcholine, serotonin, vasoactive intestinal polypeptide, substance P, and calcitonin gene-related peptide was measured during electrical field stimulation of isolated preparations of rat ileum from control and 8-wk streptozotocin-treated diabetic rats. Electrical field stimulation of the control rat ileum caused a significant increase in the release of all the above substances from the enteric nerves. The electrically evoked, but not the basal, release of these substances was inhibited by tetrodotoxin. In the diabetic rat ileum, however, there was no increase in the release of vasoactive intestinal polypeptide and calcitonin gene-related peptide during electrical stimulation, whereas endogenous release of acetylcholine, serotonin, and substance P was unaffected by the diabetic state. This was surprising in view of the increased fluorescence intensity and tissue content of vasoactive intestinal polypeptide-like immunoreactivity in the same tissue reported previously. The lack of increase in evoked release of vasoactive intestinal polypeptide in the diabetic preparations might be due to an impaired mechanism of release at the terminal site or to defective axonal transport of the peptide, whereas in the case of calcitonin gene-related peptide, it might be the result of the low level of the peptide present in the enteric nerve fibers of the diabetic rat ileum. The differential effect of diabetes on enteric nerves is discussed.
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PMID:Lack of release of vasoactive intestinal polypeptide and calcitonin gene-related peptide during electrical stimulation of enteric nerves in streptozotocin-diabetic rats. 244 15

The effect of progression of diabetes on adrenergic, serotonergic, and peptidergic innervation of the proximal colon of the rat at 8, 16, and 25 wk after induction of diabetes with streptozotocin was investigated using immunohistochemical, biochemical, and immunochemical methods. Two different responses to diabetes emerged from the present study. The first response, which involves noradrenaline and vasoactive intestinal peptide, was characterized by a sign of degeneration, where there was an initial increase in tissue level and immunoreactivity of the transmitters followed by a decrease in tissue level and density of nerve fibers at 16 and 25 wk after induction of diabetes. The second response, which involves 5-hydroxytryptamine, substance P, and calcitonin gene-related peptide, was characterized by changes in tissue level and immunoreactivity of the transmitters with no evidence of degeneration. The third feature was one of resistance to change due to diabetes, which was demonstrated by neuropeptide Y-containing nerves, where there was neither a change in tissue level of neuropeptide Y nor a change in immunoreactivity. It seems likely that the overall changes described will have profound implications in the function of the gut in the streptozotocin-diabetic rat model that may have some parallels in diabetic humans.
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PMID:Progressive changes in adrenergic, serotonergic, and peptidergic nerves in proximal colon of streptozotocin-diabetic rats. 245 87

The effects of streptozotocin-induced diabetes on the function and pattern of innervation of the rat parotid gland were investigated. An in vitro preparation was used to measure amylase release and immunohistochemistry was used to examine the innervation of the gland. Basal amylase release and the response to field stimulation were reduced in diabetic animals. In the presence of atropine or a propranolol/phentolamine mixture both control and diabetic responses were attenuated. When all 3 antagonists were present the response to field stimulation (non-adrenergic, non-cholinergic [NANC] response) was about 30% of maximal in untreated rats but virtually abolished in diabetic animals. Substance P (SP), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY) all stimulated amylase release in untreated rats. However, in diabetic rats the responses to all 3 peptides were reduced. No differences in staining were observed between control and diabetic rats with antisera to tyrosine hydroxylase, substance P. VIP or calcitonin gene-related peptide. In contrast there was a marked reduction in NPY-like immunoreactivity in the acinar tissue of diabetic rats. These data suggest that the diabetic rats had a failure of NANC transmission which appears to be due to a reduced NPY innervation and a lack of responsiveness to peptidergic (SP, VIP and NPY) agonists.
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PMID:The effects of streptozotocin-induced diabetes on the peptidergic innervation and function of the rat parotid gland. 247 75

Standardised skin biopsies followed by immunohistochemical examination for the presence of terminal nerve fibres reacting for neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) were evaluated. Healthy subjects regularly displayed free nerve endings of both fibre types in the papillary and reticular dermis. Both fibre types were present close to blood vessels, while CGRP immunoreactive fibres were more often encountered near sweat gland acini compared to SP fibres. Diabetes mellitus complicated by polyneuropathy was accompanied by marked reduction of SP and CGRP reactive fibres in the dermis layers. Five type I diabetes patients without clinical or neurophysiological evidence of polyneuropathy also had reduced density of both fibre types, being significant for CGRP fibres when compared with controls. Skin biopsy with immunohistochemical staining for neuropeptides may represent a sensitive tool in evaluation of patients with peripheral neuropathies.
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PMID:Nerve fibre studies in skin biopsies in peripheral neuropathies. I. Immunohistochemical analysis of neuropeptides in diabetes mellitus. 248 Apr

The peptide amylin (previously termed Diabetes Associated Peptide) has recently been isolated and characterised from the amyloid of the pancreatic islets of Langerhans from human type 2 diabetics. Amylin shows about 46% identity in amino acid sequence on comparison with the calcitonin gene-related peptides (CGRPs) and also shows some similarity to insulin. Recent studies have also shown that both amylin and CGRP are potent inhibitors of insulin-stimulated glycogen synthesis in skeletal muscle in vitro. Hormones may be arranged into families, therefore a degree of order exists even though hormone-mediated effects are complex. The polypeptides insulin, insulin-like growth factors (IGFs) and relaxins have been grouped into such a family with similarities both at the protein-structural and genetic levels. We now demonstrate that this insulin-related family, along with amylin and the CGRPs, are members of a peptide superfamily defined by structural similarity in the region corresponding to the A-chain of insulin. In order to distinguish this grouping of small biologically active peptides from the previous one, we have designated it the amylin superfamily. All the members of the previously defined insulin family have a region homologous to the insulin B-chain. Insulin, the IGFs, the relaxins, the CGRPs and amylin are all involved in carbohydrate metabolism and therefore these peptides are functionally as well as structurally related. This grouping of peptides may have important implications for the study of human metabolic disease.
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PMID:The amylin superfamily: a novel grouping of biologically active polypeptides related to the insulin A-chain. 249 Dec 58

Insulin-deficient diabetes causes hypothalamic and pituitary dysfunction. The possible role of hypothalamic regulatory peptides in mediating these disturbances was investigated in spontaneously diabetic BB/E Wistar rats. Concentrations of 10 regulatory peptides were measured in the central (nucleus-rich) and lateral parts of the hypothalamus in 18 diabetic and 5 non-diabetic BB/E rats. Diabetic rats were treated with either intensified or low-dose insulin schedules to achieve moderate or severe hyperglycaemia (mean blood glucose concentrations, 8 and 20 mmol l-1 respectively). Neuropeptide Y concentration and content in the central hypothalamus were increased by 30-40% in both moderately and severely hyperglycaemic diabetic groups (p less than 0.01). Lateral hypothalamic neuropeptide Y levels did not differ significantly between the groups. The only other peptide to show any significant difference between diabetic and control rats was calcitonin gene-related peptide, whose central hypothalamic concentrations were significantly increased in the severely hyperglycaemic animals. Alterations of hypothalamic neuropeptide Y, which has potent experimental effects on hypothalamo-pituitary function, may contribute to certain neuroendocrine disturbances in insulin-deficient diabetes.
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PMID:Elevated neuropeptide Y concentrations in the central hypothalamus of the spontaneously diabetic BB/E Wistar rat. 252 1


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