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)

We previously reported that sulfonylurea treatment reduces insulin (IRI), glucagon (IRG) and somatostatin (SRIF) release following metabolic stimuli from the isolated perfused pancreas of normal rats and that a reduction in IRI, IRG and SRIF pancreatic content was also observed. The present work was undertaken to investigate the effects of long-term glibenclamide treatment on the gastrointestinal content of gut hormones in normal rats. Moreover, the effects of sulfonylurea treatment on IRI, IRG, and SRIF pancreatic content were also analyzed and compared to the peripheral hormone plasma levels. Two groups of male Sprague-Dawley rats received glibenclamide (1 mg/kg/day per os; n = 14) or placebo (distilled water; n = 10) for 5 months, respectively. Tissue contents of IRI, IRG and SRIF in acid-ethanol extracts of pancreas and of gastric inhibitory peptide (GIP), vasoactive intestinal polypeptide (VIP), entero-glucagon (gut-GLI) and SRIF in acid-ethanol extracts of intestine were determined. Blood glucose and plasma pancreatic hormone levels were also measured. Glibenclamide treatment lowered the levels of IRI, IRG and SRIF in the pancreatic tissue; in the same way gut-GLI, SRIF and VIP intestinal concentrations were significantly reduced, whereas no significant inhibition was detected in intestinal GIP content. Blood glucose levels and IRI and SRIF plasma concentrations were similar in the two groups. IRG plasma levels were reduced in the sulfonylurea group. These findings might suggest that sulfonylurea suppresses hormone biosynthesis in a non-specific manner.
Diabetes Res Clin Pract 1989 Feb 15
PMID:Effects of long-term glibenclamide administration on gastrointestinal and pancreatic hormones in normal fasting rats. 249 27

Acute protein-calorie malnutrition impairs both glucose tolerance and insulin secretion, and long-term pancreatic damage leading to malnutrition diabetes has been postulated. The present study has investigated this association in rats weaned onto 5% protein (LP) or 18% protein (normal, N) diet from age 3 weeks to 6 weeks. From 6 weeks both LP and N rats were fed N diet for the remainder of the experiment. LP rats did not grow while on the LP diet and remained significantly lighter for several weeks. Nose to tail tip length was identical for the two groups in both sexes at both 24 and 48 weeks, and mean body weight was not significantly less in LP than N after 18 weeks in either sex. Protein/DNA ratios in LP (an index of cell size) remained lower than N in heart, skeletal muscle, and lung at 24 and 48 weeks, but not in gut, liver, or kidney tissues. Thus, skeletal growth was apparently not impaired by the early malnutrition, but muscle tissue did not catch up. The similarity in final body weight implies greater adipose stores in older LP rats. At 12 weeks there was no difference in glucose tolerance tests (GTT) either between males and females within a dietary group or between N and LP, despite impaired insulin secretion in LP. Both fasting glucose levels and GTT deteriorated markedly between 12 and 48 weeks in all rats, but especially in LP males. Serum insulin levels following glucose injection were lower at 48 weeks than 12 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term follow-up after early protein-calorie malnutrition in young rats: sex difference in glucose tolerance and serum insulin levels. 250 76

In the period from 1980-86 we obtained 51 strains of Listeria from meningitis in adults for serotyping and phage-typing. Ten strains were associated with meningitis and 3 with septicaemia of immunocompromised patients. They suffered from leukaemia, diabetes, Hodgkin's disease, alcoholism, lupus erythematodes. The lethality rate in these patients was 70%, in other patients with meningitis 30%. Phage typing has shown that 4b strains were often determined by the phage-code 00010 and similar codes. This phage-pattern might be specific for meningitis strains. The immunocomprised patient is especially endangered in taking up listeriae from the environment, but it must also be in consideration that listeriae may easy gain access from the gut into the vessels.
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PMID:Listeria-meningitis and -septicaemia in immunocompromised patients. 251 62

Growth hormone (GH) has long been considered to have importance in diabetes. With poor control in Type 1 diabetes GH levels are high and may aggravate poor metabolic control. Pharmacological suppression of GH release at this stage might reverse the metabolic changes, with the possible added benefit of lower plasma insulin concentrations. Diabetic patients with life-long GH deficiency rarely develop retinopathy, while pituitary ablation in patients with retinopathy often leads to improvement. Growth hormone release inhibiting factor, somatostatin, has a short plasma half-life, and multiple effects on the endocrine system and on the gastrointestinal tract, making it unsuitable for clinical use as a GH suppressant. Long-acting analogues have a long half-life, but remain non-specific in their effects. In Type 2 diabetes the analogue Octreotide suppresses insulin and glucagon release, leaving glucose levels either unchanged or somewhat elevated. Gastrointestinal side-effects have been common, but may diminish with long-term treatment. In Type 1 diabetes insulin requirement is decreased by Octreotide, but as in Type 2 diabetes GH suppression has been observed consistently only when the drug was given at bed-time. The decrease in insulin requirement may reflect suppression of glucagon release and/or gut effects. Amelioration of the 'dawn phenomenon' has not proved possible, and hypoglycaemia has proved a particular problem with Octreotide given subcutaneously at night. The lack of effective GH suppression (particularly in patients with proliferative retinopathy), lack of specificity, and the gut and hypoglycaemic side-effects, argue strongly against a clinical role for the current somatostatin analogues in diabetes mellitus.
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PMID:Somatostatin analogues in diabetes mellitus. 256 19

The activity of tyrosine hydroxylase (TOH), the rate-limiting enzyme in norepinephrine biosynthesis, was measured in selected sympathetic ganglia to develop a quantitative measure of sympathetic autonomic neuropathy in streptozocin-induced diabetic rats. Surprisingly, TOH activity was elevated twofold in diabetic prevertebral ganglia innervating the alimentary tract (i.e., superior mesenteric, celiac, and inferior mesenteric), which has terminal processes that develop neuroaxonal dystrophy in this model system. TOH activity of paravertebral ganglia (i.e., superior cervical and stellate) with nonalimentary targets was not increased in the same animals. Increased TOH activity in the prevertebral ganglia 1) developed within the 1st wk of diabetes and persisted for 10 mo, 2) did not represent a change in TOH affinity for d-1,6-methyl-5,6,7,8- tetrahydropterine cofactor, 3) was prevented by both nicotinamide pretreatment and early institution of insulin therapy, and 4) did not develop as a result of classical transsynaptic induction. Pair-feeding experiments confirmed that the most likely cause of increased TOH activity in this system was the marked hypertrophy and hyperplasia of the diabetic bowel resulting from compensatory hyperphagia. We conclude that TOH activity does not represent a suitable marker for sympathetic autonomic neuropathy in this experimental system. Rather, the increase appears to be an example of a selective increase in the synthesis of neurotransmitter enzymes, possibly in response to increased trophic support provided by the expanded target, i.e., the hypertrophic gut. The additional synthetic stress imposed on prevertebral neurons by the expansion of the innervation of the alimentary target coupled with the complex diabetic metabolic milieu may contribute to the development and selective distribution of dystrophic axonopathy to the innervation of the alimentary tract.
Diabetes 1989 Aug
PMID:Tyrosine hydroxylase activity in sympathetic nervous system of rats with streptozocin-induced diabetes. 256 57

We report a case of a 29-yr-old man with a rectal carcinoid that metastasized to the liver, secreting somatostatin. The patient first presented with an abdominal mass and mild diabetes, and, subsequently, rectal tumor and hypersomatostatinemia. Microscopic examination of the rectal tumor showed characteristic features of carcinoid. Multiple liver metastases were recognized. The plasma level of somatostatin was remarkably high (2,839 pg/ml). Plasma gut glucagon and pancreatic polypeptide (PP) increased with progress of the disease. He died of hepatic failure 20 months after his first admission. Immunoperoxidase staining showed that rectal tumor cells contained somatostatin-like-immunoreactivity. Electron microscopy of tumor tissue showed neurosecretory (D-cell) granules. Somatostatin content of the rectal tumor was very high (5,629 pg/mg).
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PMID:Somatostatinoma of the rectum. 257 69

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

Morbid obesity is a major health problem in this country and throughout the world. In addition to its social stigma (in the western world), obesity exacerbates several disease states such as diabetes, hypertension, cardiac disease and restrictive lung disease. When effective medical treatment of obesity becomes available, it will depend in part upon understanding the physiologic factors that control satiety. This review summarizes the information available on brain and gut control mechanisms of satiety. Brain nuclei located in the lateral hypothalamus, ventromedial hypothalamus, and other paraventricular areas are the sites of action for potent neuropeptides, such as cholecystokinin (CCK) and neuropeptide Y, that appear to regulate feeding. Exogenous CCK has been used clinically to decrease meal size in obese patients. The sites of the satiety cascade that are most often manipulated are the gastric and intestinal phases. Physiologic gastric distension is a potent inhibitor of feeding, whereas the intermeal interval may be regulated by intestinal signals released by food in the gut. Jejunal-ileal bypass has fallen from favor and has been replaced by gastric restrictive procedures that create a small proximal gastric pouch that empties into the small bowel (gastric bypass) or the distal stomach (gastroplasty). These operations rely partially on their ability to produce gastric distension in the proximal gastric pouch at an early stage during a meal. Thus, failure results if the pouch compensates by distending or if the stoma widens with subsequent loss of slow emptying. Improved medical and surgical treatment will be designed to intervene at specific sites of the satiety cascade as knowledge of the physiologic control mechanisms of satiety increases.
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PMID:Physiologic approaches to the control of obesity. 229 39

The rate of the small intestine amylolytic digestion appears to be a major determinant of the glycemic response. Foods such as legumes appear to be digested less rapidly than many cereal foods although even amongst these large differences in rates of in vitro digestion exist. Studies of diabetes using high fibre, high legume diets have almost uniformly noted improvements in glycemic control and blood lipid profile. However, diets where changes in fibre content have been relatively small, but where the foods were selected on the basis of their slow rates of digestion and flatter glycemic response, have also produced similar beneficial effects. The reasons for the altered rates of digestion include fibre, food form, the nature of the starch, antinutrients etc. Through reducing the rate of digestion of starchy foods post prandially "slow release" starchy foods blunt many gut hormone responses, and prolong FFA and ketone body suppression. In addition increased starch losses to the colon may enhance production of SCFA. All these events may modify carbohydrate and lipid metabolism. Many foods which produce these effects are traditional starchy foods and so strengthen current recommendations of the diabetes association, heart foundations and cancer institutes to increase the use of starchy foods through reducing fat intake. Recognition of the nutritional value of these foods is however not new, but was well accepted in the ancient world and is still preserved in traditional cultures where freedom from many of the major non-infective Western diseases is a notable phenomenon.
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PMID:Starchy foods and fiber: reduced rate of digestion and improved carbohydrate metabolism. 282 27

Prior exposure of isolated perifused rat islets to the sulfated gut hormone cholecystokinin-8 (CCK-8S) dramatically increased their insulin secretory response to 7.5 mM glucose, 10 mM arginine, and 10 mM alpha-ketoisocaproate. In the case of glucose, the heightened secretory response was still apparent 60-80 min after CCK-8S removal from the perifusion medium. Prior exposure of perifused islets to arginine (10 mM), tolbutamide (25 microM), or forskolin (1.0 microM) did not sensitize them to 7.5 mM glucose. CCK-8S exposure increased 3H efflux from islets prelabeled with [3H]inositol, and the increase in 3H efflux was sustained after CCK-8S removal from the perifusion medium. The duration of this increase in 3H efflux paralleled the temporal characteristics of this sensitization process and was significantly attenuated by 25 microM asperlicin, a competitive antagonist of CCK binding to its membrane receptor. Arginine, tolbutamide, or forskolin treatment of islets did not increase 3H efflux from [3H]inositol-prelabeled islets. The results suggest that the turnover of membrane phosphoinositides induced by CCK-8S is largely responsible for this heightened state of secretory responsiveness to various stimulants. Second-messenger molecules generated during phosphoinositide turnover may be responsible for the phenomenon of sensitization displayed by islet tissue to CCK-8S addition.
Diabetes 1987 Dec
PMID:Cholecystokinin-induced alterations in beta-cell sensitivity. Duration, specificity, and involvement of phosphoinositide metabolism. 282 61


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