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)

Twenty grafts of highly purified islets of Langerhans (mean +/- SE vol 0.98 +/- 0.3 ml, islet diam 122 +/- 5 micron) were autoimplanted into the spleen or liver of totally pancreatectomized dogs. Portal venous pressure did not change significantly. Incremental doses of islets of 1000-3000 (n = 3), 3000-4000 (n = 6), 4000-5000 (n = 5), 5000-6000 (n = 3), and 6000-8000 (n = 3) per kilogram body weight resulted in corresponding fasting plasma glucose (PG) of 258 +/- 18, 163 +/- 13, 158 +/- 17, 138 +/- 15, and 108 +/- 6 mg/dl. In 3 apancreatic control dogs, PG was 338 +/- 9 mg/dl. One (normoglycemic) dog died of wound complications, and follow-up PG at 1 mo was 89 +/- 5 mg/dl in 6 of 10 dogs that received 3000-5000 islets/kg and 91 +/- 6 mg/dl in all 6 that received greater than 5000 islets/kg. K values 1 mo after surgery during glucose tolerance tests were 1.8 +/- 0.3 for 6 spleen dogs and 1.6 +/- 0.3 for 6 liver dogs. Six months after splenic implantation, PG was 75 +/- 4 mg/dl and rose to greater than 350 mg/dl after splenectomy. These data define the critical number of purified dog islets of known size that is necessary to induce prolonged normoglycemia. Sufficient pure islets can be collected from 1 dog pancreas to correct diabetes after autoimplantation into the liver or spleen.
Diabetes 1988 Apr
PMID:Critical mass of purified islets that induce normoglycemia after implantation into dogs. 313 12

Sensitivity to insulin in vivo was studied in 8 normal weight C-peptide negative Type 1 (insulin-dependent) diabetic patients (age 23 +/- 1 years, diabetes duration 6 +/- 2 years), and in 8 age, weight and sex matched healthy subjects, using the euglycaemic clamp and 3-3H-glucose tracer technique. Prior to the study diabetic patients were maintained normoglycaemic overnight by a glucose controlled insulin infusion. Sequential infusions of insulin in 3 periods of 2 h resulted in mean steady state insulin levels of 12 +/- 2 versus 11 +/- 1, 18 +/- 2 versus 18 +/- 2 and 28 +/- 3 versus 24 +/- 2 microU/ml in diabetic patients and control subjects. Corresponding glucose utilization rates were 2.4 +/- 0.2 versus 2.4 +/- 0.1, 2.4 +/- 0.2 versus 3.0 +/- 0.3 and 2.9 +/- 0.3 versus 4.6 +/- 0.6 mg.kg-1.min-1, p less than 0.02. Portal insulin values in the three periods were calculated to 12 +/- 2 versus 25 +/- 3, 18 +/- 2 versus 32 +/- 3 and 28 +/- 3 versus 37 +/- 3 microU/ml in the diabetic patients and control subjects using peripheral insulin and C-peptide concentrations and assuming a portal to peripheral insulin concentration gradient of 1 in diabetic patients and of 2.4 in control subjects. Corresponding glucose production rates were 2.5 +/- 0.2 versus 2.4 +/- 0.1, 1.6 +/- 0.1 versus 0.9 +/- 0.2 and 0.7 +/- 0.1 versus 0.4 +/- 0.2 mg.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhanced hepatic insulin sensitivity, but peripheral insulin resistance in patients with type 1 (insulin-dependent) diabetes. 332 18

To determine the effectiveness of glucagon suppression in improving glucose homeostasis in diabetes, tracer-determined glucose kinetics were measured during a 6-h somatostatin infusion in six alloxan-diabetic dogs (moderately severe diabetes) and five depancreatized dogs deprived of insulin treatment for 3 days (prolonged severe diabetes). Plasma immunoreactive glucagon (IRG) decreased 70 +/- 9% in the alloxan-diabetic and 80 +/- 4% in the depancreatized dogs. Portal vein levels of plasma immunoreactive insulin (IRI) fell (17.0 +/- 2.3 to 4 micro.5 +/- 0.4 microU/ml) as did peripheral vein IRI levels (6.7 +/- 0.9 to 4.7 +/- 0.5 microU/ml) in the alloxan-diabetic dogs. In the depancreatized dogs plasma IRI levels were undetectable. Plasma glucose concentrations fell (278 +/- 17 to 169 +/- 12 mg/dl) during IRG suppression in the alloxan-diabetic dogs due to a rapid and sustained decrease in glucose production (Ra) (6.0 + 0.9 to 3.6 + 0.3 mg X kg-1 X min-1). Glucose disappearance (Rd) decreased gradually (5.9 + 0.6 to 3.9 + 0.2 mg X kg-1 X min-1). In contrast, in the depancreatized dogs, IRG suppression did not alter glucose concentrations or kinetics. Thus, glucagon suppression decreased glycemia by decreasing Ra only in moderately severe diabetes. However, this was associated with decreased rather than improved glucose utilization. The ineffectiveness of glucagon suppression during prolonged severe diabetes could relate to the degree and duration of the metabolic derangement and/or indicate that the continuous presence of some insulin is necessary for glucagon suppression to improve glucose homeostasis.
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PMID:Glucagon suppression improves glucoregulation in moderate but not chronic severe diabetes. 613 57

In order to assess the interrelationships between stomach and pancreas regarding the secretions of somatostatin-like immunoreactivity (SLI), glucagon (IRG), and insulin (IRI), concentrations of the three hormones were assayed in portal plasma and portal blood flow was measured in enterectomized rats before and after the selective removal of stomach or pancreas. Portal plasma SLI, IRG, and IRI concentrations were significantly increased by i.v. arginine in control rats (pancreas + stomach present). After gastrectomy, SLI, IRG, and IRI concentrations were, respectively, 52 +/- 13% (N = 15; P less than 0.005), 234 +/- 40% (P less than 0.001), and 119 +/- 15% (NS) of the pregastrectomy values. A decreased SLI secretion, an increased IRG release, and an unmodified basal IRI release were estimated by portal flow measurement. The A- and B-cell responses to arginine in the gastrectomized rats were significantly higher than in the control rats, while the D-cell response was no longer detectable. After pancreatectomy, by contrast, SLI concentrations were 360 +/- 75% of the prepancreatectomy values (N = 12; P less than 0.001). This reflected an actual increment of SLI release, taking into account the concomitant measurement of portal blood flow. The concentrations of IRG declined by 51 +/- 5% (P less than 0.001) and IRI was no longer measurable. A- and B-cell responses to arginine also were no longer detectable. These results suggest that in these experimental conditions (1) the stomach restrained pancreatic A- and B-cell responses to arginine, perhaps through the SLI released from the stomach and (2) the pancreas restrained gastric SLI secretion, perhaps through insulin.
Diabetes 1983 Aug
PMID:Reciprocal gastropancreatic modulations for the release of somatostatin-like immunoreactivity, glucagon, and insulin in the rat. 634 73

Literature on liver morphology in untreated obesity reveals varying prevalences of various pathological findings. The purpose of this literature study was to summarize and evaluate the published observations and to discuss discrepant findings. A complete search was aimed at utilizing bibliographic methods including a computerized survey. Forty-one original articles were included, comprising information on liver morphology in 1515 morbidly obese patients. Liver biopsy was considered normal in 12 per cent of the cases. The most frequent abnormality reported was fatty change, present in 80 per cent of the biopsies. Portal inflammation was also common (33 per cent). Fibrosis, mainly portal or periportal, was observed in 29 per cent. Cirrhosis, however, involved only 3 per cent. Study of relationships between the degree of liver change and certain possible pathogenetic factors (eg degree and duration of obesity, age, sex, alcohol consumption, diabetes mellitus) does not point towards a single causal factor. Co-influence of additional pathogenetic factors are likely in the development of liver changes in morbid obesity.
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PMID:Liver morphology in morbid obesity: a literature study. 637 41

In order to establish the safety and efficacy of fluoxetine in subjects over 60 years of age with Type 2 diabetes, a randomized, double-blind, parallel study of 30 obese subjects was undertaken, comparing the use of fluoxetine 60 mg daily with placebo. Subjects were diet controlled with an HbA1 < 14% (reference range 6-9%) and BMI > 29 kg m2. Those taking fluoxetine had a median weight loss of 2.6 kg at 3 months (p < 0.001) and 3.9 kg at 6 months (p < 0.02), compared with weight loss in the placebo group of 0.1 kg and 0.0 kg at 3 and 6 months, respectively. Improved glycaemic control was also demonstrated in the fluoxetine group compared with placebo, initial HbA1 levels of 8.0% vs 8.7% (NS) falling at 4 months by 0.9% (p < 0.02) and at six months by 0.9% (p < 0.02). No sustained improvement in fasting blood glucose levels was demonstrated. Reporting of adverse events was similar in both groups. Fluoxetine in the short term aids weight loss and improves glycaemic control without a significant increase in adverse events in elderly Type 2 diabetic subjects.
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PMID:A study of fluoxetine in obese elderly patients with type 2 diabetes. 764 4

The consequences of autonomic diabetic neuropathy, a common complication of chronic diabetes mellitus, have been studied mainly with regard to heart and stomach function. Since the autonomic nervous system also regulates liver carbohydrate metabolism and haemodynamics via hepatic nerves, it was the purpose of this study to examine the function of hepatic nerves in chronically diabetic rats. Diabetes was induced by i.p. injection of streptozotocin. Rat livers were perfused via both portal vein and hepatic artery. Hepatic nerves were stimulated for 2 min using a platinum electrode placed around the portal vein and the hepatic artery; in an additional stimulation phase noradrenaline was infused into the portal vein. Stimulation of hepatic nerves as well as portal noradrenaline infusion increased hepatic glucose output and reduced flow in control and in acutely (48-h) diabetic animals, which still had almost normal glycogen content. In addition stimulation also caused an overflow of noradrenaline into the caval vein. However, nerve stimulation neither increased glucose output nor decreased flow in 4-month diabetic rats. In these rats noradrenaline overflow was nearly completely abolished and hepatic glycogen content was markedly depleted. Portal noradrenaline infusion in chronically diabetic rats reduced flow to a similar extent as in controls, yet the increase in glucose output was diminished. The lack of nerve stimulation-dependent glucose output, flow reduction and noradrenaline overflow is indicative of a profound loss of function of hepatic autonomic nerves in chronically diabetic rats.
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PMID:Loss of regulation by sympathetic hepatic nerves of liver metabolism and haemodynamics in chronically streptozotocin-diabetic rats. 863 67

Fluoxetine (F) is a specific serotonin-reuptake inhibitor that has been shown to promote weight loss and improve glycemic control in obese diabetic patients. To study its long-term metabolic effect, 40 obese patients with non-insulin -dependent diabetes mellitus (NIDDM) or impaired glucose tolerance (IGT) were included in a 12-month, randomized, placebo controlled study. Patients were assigned to receive either 60 mg F or placebo (P) daily in conjunction with a 5.0-MJ/d diet (> 50% carbohydrate). Both groups showed a significant weight loss, with a nadir after 6 months without group differences (mean +/- SD: F, 10.1 +/- 10.0 kg; P, 9.4 +/- 11.5 kg). Fifteen patients from the F group and 14 from the P group completed the 12-month study without weight loss differences. Glycemic regulation improved along with the weight loss, but with a larger decline in plasma C-peptide and fasting glucose levels on the F group (P < .05). Total skeletal muscle glycogen synthase (GS) activity increased by 31% in the F group (P < .01) and by 17% in the P group (nonsignificant) after 6 months of treatment, but was still less than the activity in normal-weight controls (aged 28.0 +/- 6.3 years; body mass index, 23.5 +/- 2.2). After adjustment for fasting glucose, insulin, weight loss, and diabetic state, a positive effect of F remained on the total GS activity, which accounted for 27% of the variation (P < .05). The waist to hip ratio was reduced in P subjects as compared with F subjects (P < .05). Fat-free mass (FFM) tended to be more reduced in the F group as compared with P subjects (4.9 v 1.9 kg), although the difference did not reach statistical significance. In conclusion, F seems to improve insulin sensitivity beyond the effect mediated through weight loss by a possible effect on GS activity in skeletal muscle tissue.
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PMID:Long-term effects of fluoxetine on glycemic control in obese patients with non-insulin-dependent diabetes mellitus or glucose intolerance: influence on muscle glycogen synthase and insulin receptor kinase activity. 878 26

Growth hormone (GH) hypersecretion and relative insulin-like growth factor I (IGF-I) deficiency have been implicated in the development of insulin resistance, poor metabolic control, and impaired growth during puberty in insulin-dependent diabetes mellitus (IDDM). Portal levels of insulin are critical for the integrity of the hepatic GH receptor and suppression of the inhibitory IGF-binding protein I. Increasing insulin doses during puberty will result in adequate portal levels of insulin and thus restore IGF-I levels and IGF bioactivity, but at the risk of nocturnal hypoglycaemia and weight gain. Restoration of normal circulating levels of IGF-I using the recombinant peptide will lead to reductions in GH levels and improved insulin sensitivity. Given as a daily subcutaneous injection, low-dose recombinant human IGF-I (40 micrograms/kg/day) could prove to be a useful adjunct to standard insulin therapy during puberty in IDDM. The reduced and more stable insulin requirement might reduce the risks of nocturnal hypoglycaemia and weight gain. However, whereas intensified insulin therapy will reduce the risk of microangiopathic complications, the benefits of combination therapy have not been proven. The role of recombinant human IGF-I in the treatment of IDDM needs to be tested by long-term controlled trials.
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PMID:Growth hormone insulin-like growth factor I axis in insulin-dependent diabetes mellitus. 885 34

Depression is a common, life-disrupting, potentially lethal illness that can affect both sexes and all ages. Its peak onset is in the early adult years. It is more common than hypertension in primary care practice. Recent studies show that fewer than 1 in 20 depressed patients are correctly diagnosed and adequately treated. Depression periodically destroys the productivity of those with the condition, and depressed patients have a worse quality of life than patients with debilitating, chronic conditions such as arthritis, hypertension, diabetes mellitus and back pain. Suicide occurs in as many as 15% of patients with depression, especially those with recurrent episodes and hospitalisations, and may even occur in those with in subsyndromal depression. Suicide is one of the leading causes of death, and individuals who complete suicide have usually experienced mood disorders, mainly depression. Current data support a decreased frequency of suicidal ideation with all antidepressants, including selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). Modern pharmacotherapy is the cornerstone for effective treatment of depression. As they are well tolerated, even in the presence of comorbid medical illness, and easier to manage, SSRIs enhance compliance. A fully adequate antidepressant dosage is suitable for patients of all ages and can be used by non-psychiatrist physicians for the treatment of the acute episode, as well as the frequent recurrences that often require long term maintenance antidepressant medication. SSRIs have fewer drug interactions than older antidepressants, and even the SSRI inhibition of hepatic cytochrome P450 enzymes has proven only very infrequently to be of clinical importance. SSRIs also effectively treat anxious depression, dysthymia and atypical depression. Fluoxetine may provide more rapid onset of therapeutic effect because it can be started at closer to its usual full therapeutic dosage than other SSRIs or older antidepressants. SSRIs, in particular fluoxetine, are more suitable for use as long-term maintenance therapy in these chronic relapsing diseases. These factors and the high efficacy rate, increased safety in overdose, reduced incidence of adverse effects (mostly decreasing with time) and superiority in ease of maintaining patients in adequate treatment plans provides fluoxetine with an overall superior therapeutic profile.
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PMID:Risks and benefits of selective serotonin reuptake inhibitors in the treatment of depression. 946 88


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