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)

G protein-mediated effects on cAMP production were evaluated in the corpus striatum of diabetic rats 5 and 14 weeks after alloxan injection by measuring both D1-receptor-induced stimulation and D2-receptor-mediated inhibition of adenylate-cyclase activity. At 5 weeks of diabetes, no obvious alterations of G protein functions were detected. Both dopamine-stimulated adenylate cyclase and bromocriptine-induced inhibition of enzyme activity were indeed similar in control and diabetic animals. Fourteen weeks after alloxan injection, profound alterations were observed. Dopamine-stimulated cAMP production was markedly increased in diabetic rats, whereas bromocriptine ability to reduce cAMP formation was almost abolished at this late stage of diabetes. Hypoactivity of Gi/Go proteins was also confirmed by the reduced ability of the GTP non-hydrolyzable analog GTP-gamma-S to inhibit forskolin-stimulation of adenylate cyclase. These results show an apparent functional imbalance between Gs and Gi/Go-mediated transduction mechanisms, with an increased efficacy of Gs activity likely due to the loss of Gi/Go inhibitory functions. Concomitantly with such transductional alteration detected in chronic diabetes, we observed a marked increase of the striatal content of met-enkephalin, which is known to utilize Gi/Go proteins for inhibition of adenylate cyclase. The measurement of other transmitters (vaso-active intestinal peptide, substance P, serotonin, noradrenaline, and dopamine) did not reveal any difference with respect to controls. The observed transductional defect in diabetic animals and the increased content and/or hyperinnervation by the metenkephalinergic system could be correlated as mutual compensatory mechanisms.
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PMID:Denervation and hyperinnervation in the nervous system of diabetic animals: III. Functional alterations of G proteins in diabetic encephalopathy. 251 14

Sulphonylurea drugs have been shown to augment glucose metabolism by both pancreatic and extrapancreatic actions. The regulation of glucose involves a modification of beta-endorphin secretions via central and peripheral mechanisms. beta-Endorphin participates in the regulation of feeding and is implicated both in obesity and diabetes mellitus. This study shows that glipizide could exert its pharmacological action in genetically diabetic (db/db) mice via beta-endorphin secretions by a central mechanism.
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PMID:Effects of glipizide on beta-endorphin concentration in the brain of genetically diabetic (db/db) mice. 253 Jan 22

The genetically obese mouse (C57BL/6J ob/ob) is a commonly used animal model of non-insulin-dependent diabetes mellitus. These mice show exaggerated glycemic responses during behavioral stress and adrenergic stimulation, but the precise glucoregulatory mechanisms are not well characterized. The ob/ob mice have multiple endocrine abnormalities, including elevated pituitary and circulating beta-endorphin levels; and a relationship between hyperglycemia and altered opioid function has been suspected. We now report that opiate antagonism with naltrexone potentiates hyperglycemic responses during stress and epinephrine challenge in obese mice. This effect of opioid blockade suggests that endogenous opioids inhibit stress- and epinephrine-induced hyperglycemia in the genetically obese mouse.
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PMID:Naltrexone potentiates glycemic responses during stress and epinephrine challenge in genetically obese mice. 254 57

Peripheral neuropathy is a correlate of experimental diabetes induced in rats by means of a single injection of alloxan. The autonomic and enteric innervation of the gut are profoundly affected in the small intestine of such animals. A complex process of denervation and hyperinnervation of the gut wall of diabetic animals is observed. It was previously reported that the cholinergic parasympathetic innervation of the intestine is markedly reduced. We have found that noradrenergic sympathetic axons hyperinnervate the duodenum of diabetic rats, whereas noradrenaline levels are significantly reduced in the jejunum. The putative enteric neurotransmitter dopamine is also present in higher levels in the duodenum. The intrinsic peptidergic neurons of the gut are deeply affected as well in diabetic rats. Substance P and met-enkephalin content are remarkably reduced throughout the small intestine, whereas vasoactive intestinal polypeptide levels (VIP) are significantly increased in the duodenum. Indeed, immunocytochemical staining of the ileum did reveal hypertrophy of VIP-positive axons in diabetic rats. The intrinsic serotoninergic innervation of the gut is apparently unaffected. Our results indicate that the changes of gut innervation observed in experimental diabetes are consistent with increased content and also likely with hyperinnervation by the neuronal systems involved in smooth muscle relaxation and decreased content and with denervation by those systems with smooth muscle contraction properties. Such a perturbed gut innervation may be responsible of the gastrointestinal dysfunctions that are among the most common complications of diabetes.
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PMID:Denervation and hyperinnervation in the nervous system of diabetic animals. I. The autonomic neuronal dystrophy of the gut. 259 79

Products of the pro-opiomelanocortin gene have been shown to have marked effects on insulin secretion. Selective antagonists of beta-endorphin have been reported to correct the impaired insulin secretory response to glucose seen in non-insulin dependent diabetes. Families with an autosomal dominant pattern of inheritance of diabetes were studied for possible linkage between diabetes and the pro-opiomelanocortin locus by examining the inheritance of a Rsa 1 restriction fragment length polymorphism. In two families with classical Type 2 diabetes there were recombinants between the disease and the pro-opiomelanocortin locus. In a family with maturity-onset diabetes of the young there were only two informative meoises, but there was a crossover between the disease and the pro-opiomelanocortin gene locus. Inherited defects in or near the pro-opiomelanocortin gene locus are unlikely to be directly involved in the aetiology of non-insulin dependent diabetes.
Diabetes Res 1989 Mar
PMID:Analysis of the pro-opiomelanocortin gene in non-insulin dependent diabetic families. 280 86

A lipolytic activity for beta-endorphin (beta EP) has been recently suggested both in vitro and in vivo. In our study we evaluated the relationship between beta EP and blood lipid pattern in Type 2 (non-insulin dependent) diabetic patients. Plasma beta EP, together with plasma beta-lipotropin (beta LPH), ACTH, cortisol and plasma insulin (IRI), was measured by RIA after silicic acid plasma extraction and Sephedex G-75 column chromatography. Although reduced beta EP (7.12 +/- 3.8 fmol/ml) and increased beta LPH (9.3 +/- 3.7 fmol/ml) levels were found in diabetic patients, compared to controls (8.53 +/- 3.3 fmol/ml, p less than 0.05 and 8.34 +/- 2.6 fmol/ml, p less than 0.05, respectively), higher plasma beta EP concentrations were demonstrated in hyperlipidemic diabetic patients (10.3 +/- 3.9 fmol/ml) than in patients with normal blood lipid pattern (4.85 +/- 1.45 fmol/ml, p less than 0.001). Several positive correlations between beta EP, plasma free fatty acids (r = 0.75, p less than 0.001), triglycerides (r = 0.84, p less than 0.001) and VLDL (r = 0.80, p less than 0.001) were found in our patients independently of overweight, hypoglycemic treatment, plasma IRI levels and of the degree of metabolic control. A higher prevalence of micro- and macrovascular complications was demonstrated in hyperlipidemic than in normolipidemic patients. Blood lipid disorders might therefore be associated with increased plasma beta EP levels in Type 2 diabetes.
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PMID:Plasma beta-endorphin, free fatty acids and blood lipid changes in type 2 (non-insulin dependent) diabetic patients. 283 29

Patients with functional amenorrhea have raised central dopaminergic activity and opioid-mediated GnRH inhibition leading to inhibition of hypothalamic-pituitary-ovarian function. In the present study, basal serum cortisol and ACTH levels were measured in normoprolactinemic amenorrheic patients with (N = 14) and without (N = 7) insulin-dependent diabetes mellitus. Basal serum cortisol levels was significantly (P less than 0.01) elevated in patients with normoprolactinemic amenorrhea compared with normal women. Basal serum cortisol was significantly (P less than 0.02) elevated in amenorrheic diabetic patients compared with menstruating diabetic women. In the amenorrheic groups both cortisol and ACTH levels increased significantly (P less than 0.01) after dopamine D-2 receptor blockade, whereas no hormonal changes occurred in the control groups. It is concluded that patients with normoprolactinemic amenorrhea have elevated basal serum cortisol, the reason probably being hypersecretion of corticotropin-releasing hormone. Secondly that dopaminergic blockade with metoclopramide stimulates ACTH and cortisol secretion in patients presumed to have raised dopaminergic activity.
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PMID:Cortisol secretion in patients with normoprolactinemic amenorrhea. 284 Jul 94

A 45-year-old man with type I diabetes mellitus of 25-yr duration and well controlled by conventional insulin therapy developed an isolated adrenocorticotropic hormone (ACTH) deficiency. He presented with a 3-month history of weight loss, weakness, anorexia and persistent tendency to hypoglycemia that he had never experienced before. Basal and dynamic endocrine testing disclosed absent cortisol secretion caused by an isolated ACTH deficiency due to a primary pituitary defect. Corticosteroid replacement therapy allowed again a good glycometabolic control. The possible causes of hypoglycemia in insulin-treated diabetes and the pathogenetic basis of the reported association are discussed.
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PMID:Development of isolated ACTH deficiency in a man with type I diabetes mellitus. 284 79

Acute insulin-induced hypoglycaemia in humans provokes autonomic neural activation and counterregulatory hormonal secretion mediated in part via hypothalamic stimulation. Many patients with Type 1 (insulin-dependent) diabetes have acquired deficiencies of counterregulatory hormonal release following hypoglycaemia. To study the integrity of the hypothalamic-pituitary and the sympatho-adrenal systems, the responses of pituitary hormones, beta-endorphin, glucagon and adrenaline to acute insulin-induced hypoglycaemia (0.2 units/kg) were examined in 16 patients with Type 1 diabetes who did not have autonomic neuropathy. To examine the effect of duration of diabetes these patients were subdivided into two groups (Group 1: 8 patients less than 5 years duration; Group 2: 8 patients greater than 15 years duration) and were compared with 8 normal volunteers (Group 3). The severity and time of onset of hypoglycaemia were similar in all 3 groups, but mean blood glucose recovery was slower in the diabetic groups (p less than 0.01). The mean responses of glucagon, adrenaline, adrenocorticotrophic hormone, prolactin and beta-endorphin were similar in all 3 groups, but the mean responses of growth hormone were lower in both diabetic groups than in the normal group (p less than 0.05). The mean increments of glucagon and adrenaline in the diabetic groups were lower than the normal group, but these differences did not achieve significance; glucagon secretion was preserved in several diabetic patients irrespective of duration of disease. Various hormonal responses to hypoglycaemia were absent or diminished in individual diabetic patients, and multiple hormonal deficiencies could be implicated in delaying blood glucose recovery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Counterregulatory hormonal responses to hypoglycaemia in type 1 (insulin-dependent) diabetes: evidence for diminished hypothalamic-pituitary hormonal secretion. 285 69

The effect of met-enkephalin and the opiate antagonist, naloxone, on somatostatin and insulin secretion from the isolated, perfused rat pancreas has been studied during perfusion with 300 mg/dl glucose. In response to a gradient of met-enkephalin from 0 to 10(-5) M, release of somatostatin was inhibited at low concentrations and stimulated at high concentrations. However, both low and high concentrations of metenkephalin stimulated insulin secretion. A gradient of met-enkephalin from 0 to 10(-6) M caused only an inhibition of somatostatin release, whereas insulin release was stimulated. The effects of met-enkephalin on somatostatin release were antagonized by naloxone (10(-6) M). The metenkephalin-induced insulin secretion was partially, but not completely, blocked by naloxone. Naloxone (10(-6) M) alone changed the endocrine secretions by decreasing somatostatin release and by stimulating insulin release. Met-enkephalin may, therefore, be a physiologic regulator of pancreatic endocrine secretion.
Diabetes 1985 Dec
PMID:The effect of met-enkephalin and naloxone on somatostatin and insulin secretion from the isolated, perfused rat pancreas. 286 28


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