Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

In this study, we compared the effects of islet amyloid polypeptide (IAPP) and calcitonin gene-related peptide (CGRP) on glucose metabolism both in vivo and in vitro in the rat. Intravenous injection of rat CGRP caused a significant increase in plasma glucose concentration with a simultaneous increase in plasma insulin levels, whereas neither IAPP-NH2 nor IAPP-COOH had any effect. Moreover, intravenous infusion of CGRP decreased tolerance to intragastric administration of glucose (O-GTT) without altering plasma insulin levels, but again IAPPs had no effect. On the other hand, 125I-[Tyr0]rat CGRP specifically bound to the liver plasma membrane, and not only CGRP but also IAPP-NH2 dose-dependently displaced the specific binding of 125I-[Tyr0] CGRP, whereas IAPP-COOH had no effect. Conversely, CGRP as well as IAPP-NH2 but not IAPP-COOH evoked dose-dependent activation of adenylate cyclase in the membranes, and these effects were significantly inhibited by a CGRP receptor antagonist, human CGRP-I(8-37). However, neither CGRP nor IAPP-NH2 had any effect on glucose production in rat isolated hepatocytes. These results suggest that (1) IAPP-NH2 but not IAPP-COOH induces adenylate cyclase activation via CGRP receptors on rat liver plasma membranes, and (2) CGRP might not involve its action on the liver in the changes of glucose metabolism.
Diabetes Res Clin Pract 1992 Jan
PMID:Effects of islet amyloid polypeptide (amylin) and calcitonin gene-related peptide (CGRP) on glucose metabolism in the rat. 154 Dec 37

Members of three families with maturity onset diabetes of youth (MODY) and seven with "common" type 2 diabetes were typed for six DNA markers (H-RAS, INS, HBBC, PTH, CALC1, CAT) on the short arm of chromosome 11. Using conventional pairwise linkage analysis, close linkage in the MODY families was excluded for all six markers. By multipoint analysis and a genetic map of the short arm of chromosome 11, MODY was excluded from a region of at least 35 and up to 60 centiMorgans (cM) on the short arm of chromosome 11. Multipoint analysis in the type 2 families also excludes linkage to the INS, H-RAS region of at least 3 and up to 30 cM. This study using multipoint linkage analysis in non-insulin dependent diabetes provides strong evidence against a role for mutations in or around the insulin gene in the causation of MODY or type 2 diabetes in the families studied.
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PMID:Multipoint linkage analysis of the short arm of chromosome 11 in non-insulin dependent diabetes including maturity onset diabetes of youth. 158 33

Neuropeptides in perivascular nerves of vasa nervorum supplying blood to rat optic, sciatic, vagus and sympathetic chain nerve trunks are differentially vulnerable to streptozotocin (STZ)-induced diabetes. Immunohistochemical analysis of epineurial/perineurial nerve sheaths showed that 8 weeks after induction of diabetes, the density of neuropeptide Y (NPY)-immunoreactive nerve fibres in optic nerve sheaths was increased, while it was decreased in sciatic, vagus and sympathetic nerve sheaths. Vasoactive intestinal polypeptide (VIP)-immunoreactivity was increased in vasa and nervi nervorum of optic, sciatic, vagus and sympathetic chain nerve sheaths. Immunoassay of NPY confirmed increased levels in optic nerve sheaths and showed that substance P and calcitonin gene-related peptide levels increased in sciatic but not optic nerve sheaths. Neuropeptide levels in the intrafascicular nerve fibres were unaffected. This provides further evidence for a disturbance in the autonomic control of blood flow to peripheral and cranial nerve trunks via vasa nervorum in STZ-induced diabetes, which may lead to ischaemic changes, alter local axon reflexes and contribute to the pathogenesis of the disease.
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PMID:Differential vulnerability of neuropeptides in nerves of the vasa nervorum to streptozotocin-induced diabetes. 163 9

The effect of streptozocin diabetes on the distribution of adrenergic and peptidergic nerves in the submucous plexus of rat ileum was investigated and compared with the changes in the myenteric plexus of the same region of ileum. There was an increase in the intensity of immunoreactivity in vasoactive intestinal polypeptide- and neuropeptide Y-like immunoreactive nerve fibers and neurons and a decrease in calcitonin gene-related peptide-like immunoreactivity but no change in substance P- and dopamine beta-hydroxylase-like immunoreactivity in the nerve fibers and neurons of the submucous plexus of both 8- and 16-wk streptozocin-diabetic rat ileum. However, in the myenteric plexus of the diabetic rat ileum, there was enlargement of varicosities and an increase followed by a slight decrease in the intensity of immunoreactivity of vasoactive intestinal polypeptide- and dopamine beta-hydroxylase-like immunoreactive nerve fibers and neurons, increased substance P-like immunoreactivity in diabetes at 16 wk, and an initial decrease (at 8 wk) followed by a recovery of calcitonin gene-related peptide-like immunoreactivity at 16 wk, but no change in neuropeptide Y-like immunoreactivity. The markedly different changes in peptidergic and adrenergic nerves between the two enteric plexuses show that diabetic neuropathy induced by streptozocin is not selective and involves factors other than neurotransmitter types.
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PMID:Changes in adrenergic and peptidergic nerves in the submucous plexus of streptozocin-diabetic rat ileum. 169 44

We have previously shown depletion of nerves and neuropeptides in skin biopsies of diabetic patients, even in the absence of clinical signs and symptoms of sensory and autonomic neuropathy, but were unable to examine the changes occurring at an early stage of the disease. Therefore, the distribution and relative density of peptide-containing nerves was studied in streptozotocin-treated rats in order to assess the progression of neural changes in the initial stages of diabetes. Skin samples dissected from the lip and footpad of diabetic rats, 2, 4, 8 and 12 weeks after streptozotocin injection and age matched controls were sectioned and were immunostained with antisera to the neuropeptides substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY), and to a general neural marker, protein gene product 9.5 (PGP 9.5). No change was apparent in the distribution or relative density of immunoreactive cutaneous nerve fibres 2, 4 and 8 weeks after streptozotocin treatment. By 12 weeks there was a marked increase in the number of CGRP-immunoreactive fibres present in epidermis and dermis, and of VIP-immunoreactive fibres around sweat glands and blood vessels. A parallel increase was seen in nerves displaying PGP 9.5 immunoreactivity. No differences were detected in nerves immunoreactive for either substance P in the epidermis and dermis, and NPY around blood vessels. The alterations in the peptide immunoreactivities may be similar in the initial stages of human diabetes.
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PMID:Early increase in CGRP- and VIP-immunoreactive nerves in the skin of streptozotocin-induced diabetic rats. 170 1

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

Human calcitonin gene-related peptide (hCGRP-1) and human amylin (hA) have been reported to increase hepatic glucose output in vivo and to bind with high affinity to rat liver plasma membranes, resulting in increased cAMP production. These observations have led to the hypothesis that CGRP or amylin may be physiological regulators of liver glucose metabolism. Liver plasma membranes are derived from several cell types, including parenchymal (hepatocyte), Kupffer, endothelial, lipid storage, and smooth muscle cells. Because the parenchymal cell is responsible for the contribution of the liver to whole-body glucose homeostasis, it is important to verify the location and activity of the CGRP/amylin receptor to this cell. These studies separate liver cells prepared by collagenase digestion into parenchymal and nonparenchymal fractions by metrizamide gradient and differential centrifugation. 125I-labeled [Tyr-0]hCGRP-1 bound with high affinity to nonparenchymal cell fraction and was displaced by both hCGRP-1 and hA. hCGRP-1 bound with greater affinity than hA (Kd = 2.1 +/- 1.6 x 10(-11) vs. 2.6 +/- 1.2 x 10(-8) M) in a manner similar to the binding reported for liver plasma membrane fraction. Linear regression of receptor concentration against nonparenchymal cell count per milliliter was significant (r = 0.999, P = 0.026), leading to an estimate of 3000 receptors/cell. The parenchymal cell fraction bound very little 125I-[Tyr-0]hCGRP-1, and regression of receptor concentration against parenchymal cell count per milliliter was not significant (r = -0.708, P = 0.29), suggesting that binding was not due to parenchymal cells but instead to contamination by nonparenchymal cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Mar
PMID:Presence of liver CGRP/amylin receptors in only nonparenchymal cells and absence of direct regulation of rat liver glucose metabolism by CGRP/amylin. 184 87

The islet amyloid polypeptide (IAPP) was originally identified by chemical analysis of the amyloid component in a human pancreatic islet cell tumor. It consists of 37 amino acids and displays about 50% homology with the neuropeptide calcitonin gene-related peptide (CGRP). In the pancreatic islets the IAPP is confined to the beta-cells, co-stored with insulin in the secretory granules and apparently co-secreted with insulin on glucose stimulation. In beta-cell depletion states such as streptozotocin diabetes in animals and in human type I diabetes mellitus both the IAPP and the insulin levels display reduction or are even absent. Within the mature IAPP molecule the amino acid sequence 23-29 shows considerable amino acid heterogenicity among various mammalian species. The amino acid composition of human IAPP in this specific region promotes the development of pancreatic islet amyloidosis, a phenomenon related to the ability to develop type II diabetes in that particular species. However, as type II diabetes is an inherited disease affecting a subpopulation of humans, not only the gene coding mature IAPP, but also one or several other hereditary factors of unknown origin are needed for the disease to develop. We have established a radioimmunoassay for plasma measurements of IAPP. During screening investigations of a large material of endocrine tumors we found a patient with extremely elevated plasma levels of IAPP, about 20,000 pmol/l. Immunohistochemical investigations confirmed the IAPP content and also revealed amyloid deposits. While performing an oral glucose tolerance test insulin levels remained unchanged whereas there was an increase in the glucose and IAPP levels. It is thus concluded that IAPP can be used as a tumor marker in pancreatic islet cell tumors and that high plasma levels of IAPP can inhibit glucose stimulated insulin secretion.
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PMID:Islet amyloid polypeptide (IAPP). A short review. 185 2

Rat synthetic amidated islet amyloid polypeptide (IAPP) was infused into conscious Long-Evans rats chronically instrumented for the measurement of regional hemodynamics. Rat IAPP (0.25-2.5 nmol.kg-1.min-1) had dose-dependent tachycardiac and hypotensive effects. Renal blood flow increased at all dose levels in association with incremental rises in renal vascular conductances. Hindquarters blood flow and vascular conductance increased at the higher dose levels, but mesenteric blood flow fell with mean arterial blood pressure (i.e., there was no change in mesenteric vascular conductance). Concurrent infusion of 25 nmol.kg-1.min-1 human alpha-calcitonin gene-related peptide (CGRP) (8-37) abolished the hypotensive, tachycardiac, and renal and hindquarters vasodilator effects of rat IAPP, and during administration of both peptides, there was a transient renal and sustained mesenteric vasoconstriction. When the infusion of human alpha-CGRP (8-37) was stopped, the effects of the continued infusion of rat IAPP were reestablished. The results indicate that the reported ability of IAPP to induce insulin resistance cannot be due to decreased skeletal muscle blood flow. In addition, human alpha-CGRP (8-37) is an effective antagonist of the hemodynamic actions of rat IAPP. Because it has been shown previously that human alpha-CGRP (8-37) antagonizes the hemodynamic effects of human alpha-CGRP, these results, collectively, indicate that human alpha-CGRP and rat IAPP might act on the same receptor at which human alpha-CGRP (8-37) is an effective antagonist or that the latter is a nonselective antagonist of separate receptors on which human alpha-CGRP and rat IAPP act.
Diabetes 1991 Aug
PMID:Antagonistic effect of human alpha-calcitonin gene-related peptide (8-37) on regional hemodynamic actions of rat islet amyloid polypeptide in conscious Long-Evans rats. 186 May 59

To test the hypothesis that calcitonin (CT) deficiency may contribute to bone mineral loss in insulin-dependent diabetes mellitus (IDDM), we studied basal and calcium stimulated (2 mg/kg body wt. in 5 min) CT levels in 15 children with IDDM and osteopenia. Ten age-sex matched healthy children were studied as controls. Since extractable CT (exCT) allows more sensitive and specific measurement of CT monomer, we measured both total serum CT (tCT) and exCT. Diabetic children had slightly but significantly (P less than 0.05) higher basal levels of both tCT (24.5 +/- 7.1 ng/l) and exCT (5.6 +/- 1.6 ng/l) than controls (tCT: 18.7 +/- 5.4 ng/l; exCT: 4.3 +/- 1.2 ng/l). Calcium stimulation test pointed out significant increase (P less than 0.001) of tCT and exCT in both groups with peak values not significantly different in IDDM in respect to controls. However, diabetic children showed a reduced CT reserve evidenced by a lower peak/basal ratio (diabetics: tCT 1.68, exCT 1.84; controls: tCT 2.49, exCT 2.88) and by a more rapid decrease in CT levels. We conclude that CT deficiency is not a causative factor of diabetic osteopenia. The slightly higher basal CT values suggest that an increased bone reabsorption may be operative in IDDM and it stimulates CT secretion. This chronic "C" cell stimulation may induce the reduction in CT reserve observed employing the calcium infusion test.
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PMID:Calcitonin secretion in children with insulin-dependent diabetes mellitus. 191 95


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