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)

Plasminogen Activator Inhibitors (PA Inhibitor) have recently been identified in plasma. They are directed against t-PA and Urokinase. Two PA Inhibitors have been described: PA Inhibitor 1 from endothelial cells, hepatocytes and platelets and PA Inhibitor 2 from placenta. Enzymatic assays have been developed. They show that plasma levels of PA Inhibitor are very low under normal conditions, but a considerable increase (X10 or 20) is found in several pathological conditions (thrombo embolic disease, atherosclerosis, thrombotic risk factors (obesity, hypertriglyceridemia, diabetes) inflammatory syndrome, post operative period for PA Inhibitor 1, and in some physiological conditions (pregnancy for PA Inhibitor 2). These results plead for a pathogenic role of PA Inhibitor 1 in the development of thrombosis. Pharmacological products able to decrease the plasma level of PA Inhibitor are as yet scarce. Stanozolol, an anabolic steroid, some biguanides such as Metformin possess this property.
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PMID:[Anti-activator inhibitors of plasminogen]. 311 99

After ingestion of metformin, a drug of the biguanide class, there are gastrointestinal effects in the form of nausea and vomiting, and about 30% of the drug is recovered in feces. The purpose of this work was to explain these two phenomena. Two sets of experiments were carried out. Study I evaluated the gastroduodenal (GD) absorption in six healthy volunteers by means of an intubation method, employing a twin-lumen tube introduced into the intestine and another into the stomach. Metformin 1 g was introduced into the stomach with a homogenized meal containing a non-absorbable marker, 14C-PEG 4000; another marker, PEG 4000, was perfused continuously into the duodenum at the ampulla of Vater. Samples of GD contents were collected every 15 min during 4 h. Metformin was poorly absorbed from the stomach, about 10% over a 4-h period. It did not modify the gastric emptying of a meal but induced a duodeno-gastric reflux in five out of six subjects. About 20% of the amount of drug emptied from the stomach were absorbed from the duodenum. The delivery process was the rate-limiting factor for metformin absorption from the duodenum. The AUC/24 h increased as the absorption rate from the duodenum increased. Study 2 investigated in six healthy volunteers, using another intestinal perfusion technique, the jejunal and ileal absorption of metformin. Metformin 400 mg in saline solution was perfused, over a 2-h period, below an inflated balloon, directly into either the jejunum or the ileum.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res Clin Pract 1988 Feb 19
PMID:Metformin in the digestive tract. 335 23

Metformin, a biguanide antidiabetic agent that can be administered either alone or in combination with sulfonylureas, has been extensively used in Europe and Canada. The mechanism of action of metformin and other biguanides is not completely understood, but recent in vitro and in vivo studies suggest that metformin may act in part by both increasing the binding of insulin to its receptor and potentiating insulin action. Metformin, because of its chemical structure, does not interact with the liver and has a short half-life. Consequently, lactic acidosis, which is a rare complication of metformin, has not been associated with the proper use of this drug. In addition to its antidiabetic actions, metformin causes weight loss in obese diabetic patients and may be useful in managing associated lipid disorders.
Diabetes Care
PMID:Role of metformin in treatment of diabetes mellitus. 355 9

Metformin (Met) is a biguanide oral hypoglycemic agent used in the treatment of noninsulin-dependent diabetes mellitus (NIDDM). To define whether the glucose-lowering effects are mediated via alterations of insulin receptors, the effects of Met in vitro in rat adipocytes and in vivo in patients with poorly controlled NIDDM were studied. In vitro exposure of rat adipose tissue to metformin for 20 h resulted in a significant increase in insulin binding (mean +/- SEM percent specific [125I]insulin bound per 10(5) adipocytes: control, 1.35 +/- 0.13; Met, 1.69 +/- 0.18; P less than 0.02). No change occurred after 2 h of exposure or less. In contrast, after only 1 h of preincubation. Met alone stimulated [U-14C]glucose oxidation by 58 +/- 15.5% (P less than 0.01). Met did not stimulate glucose oxidation in the presence of a high insulin concentration. For the in vivo studies, oral glucose tolerance tests and monocyte [125I]insulin binding assays were performed before and after 7 days of Met treatment (2 g/day) in 18 patients with poorly controlled NIDDM. All patients responded to Met with a decrease in fasting and postglucose plasma glucose concentrations, but no change in insulin concentrations [pre-Met vs. post-Met: fasting plasma glucose, 210 +/- 10 vs. 157 +/- 11 mg/dl (P less than 0.001); fasting plasma insulin, 20.3 +/- 3.1 vs. 18.4 +/- 2.0 microU/ml]. When insulin binding was examined, 8 patients with decreased binding each responded to Met with a 50% or greater increase (group 1), while 10 patients with normal binding had no increase after treatment (group 2). However, both groups had similar lowering of glucose concentrations [fasting plasma glucose: group 1, 205 +/- 19 vs. 153 +/- 20 (P less than 0.001); group 2, 214 +/- 11 vs. 160 +/- 13 (P less than 0.001)]. We conclude that 1) Met has an acute insulin-like effect in vitro independent of its ability to increase insulin binding; 2) Met acts in vivo predominantly at a postreceptor site to lower plasma glucose; 3) the glucose-lowering effect is independent of pretreatment insulin binding status; and 4) the increase in insulin binding after Met treatment in patients with NIDDM and low insulin binding occurs without changes in insulin concentrations.
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PMID:Mechanism of action of metformin: insulin receptor and postreceptor effects in vitro and in vivo. 374 4

Metabolic abnormalities occur in biguanide-treated diabetic patients. We investigated the relationship between plasma metformin and phenformin concentrations and metabolic effects. Drug levels were measured in 37 type II diabetic patients by HPLC. The method was sensitive, specific, and linear over a wide range of drug concentrations. Metformin and phenformin values ranged from 236 to 718 ng/ml and from 28 to 114 ng/ml, respectively. The plasma metformin level was correlated with triglycerides (r = -0.55; P less than 0.05) but not with drug dosage, plasma glucose, HbA1, creatinine, creatinine clearance, lactate, pyruvate, lipid, and clinical parameters. Plasma phenformin concentrations correlated with lactate (r = 0.49; P less than 0.05) and HbA1 (r = 0.50; P less than 0.05) but not with drug dosage, parameters of diabetes control, creatinine, creatinine clearance, pyruvate, and clinical parameters. The clinical usefulness of this HPLC method, the evidence that the increase of lactate is related to the circulating phenformin levels, and the demonstration that the metformin effect on triglyceride metabolism is correlated to plasma drug levels are the positive findings of this work.
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PMID:Plasma biguanide levels are correlated with metabolic effects in diabetic patients. 382 80

In a questionnaire-based survey of 285 randomly selected diabetic patients, diarrhea was found to occur in 8%; this was found to be similar to that in 150 nondiabetic control patients attending other medical clinics (8%). When the diabetic patients were divided into separate therapeutic groups, metformin-treated (with or without sulfonylureas) patients had a markedly greater prevalence of diarrhea (20%) than those not on this drug (6%). A majority of patients with metformin-associated diarrhea had soiling of clothes as a problem, while at least two complained of frank loss of control over their anal sphincter. These patients did not have autonomic neuropathy, and in all who stopped this drug, diarrhea settled within 2-5 days. Only 6% of insulin-dependent diabetic individuals (IDD) had diarrhea, one of whom had explosive nocturnal stools with incontinence and features diagnostic of autonomic neuropathy. Metformin is by far the commonest cause of diarrhea and incontinence in our diabetic clinic, where it is used routinely. In contrast, diarrhea due to autonomic neuropathy is rare.
Diabetes Care
PMID:Diarrhea and metformin in a diabetic clinic. 633 43

We studied the effect of metformin therapy (1700 mg daily) on glucose tolerance, insulin secretion, and insulin binding to monocytes in 10 non-insulin-dependent diabetics (mean duration of disease 2.6 yr) who were treated for 4 wk with either metformin or placebo in a double-blind cross-over study. Metformin induced a significant decrease of glucose levels during an oral glucose load compared with placebo treatment (P less than 0.001). All patients studied showed normal or elevated basal insulin and C-peptide levels; their responses to an oral glucose load, however, were relatively hypoinsulinemic without any significant difference between metformin and placebo. Insulin binding to monocytes was nearly identical at all insulin concentrations tested in the placebo or metformin therapy phase. These data indicate that the glucose-lowering potency of metformin in non-insulin-dependent diabetics cannot be associated with changes in receptor number or affinity. It is suggested that metformin might have a positive influence on postreceptor defects in non-insulin-dependent diabetics.
Diabetes 1983 Dec
PMID:Insulin receptor binding to monocytes, insulin secretion, and glucose tolerance following metformin treatment. Results of a double-blind cross-over study in type II diabetics. 636 Jul 56

We evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific 125I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin (850 mg orally, b.i.d., for 4 days). Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects (+ 31%, P less than 0.05) and diabetic patients (+ 63%, P less than 0.01). Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded. By this mechanism, therefore, metformin may contribute to restoring insulin effectiveness in subjects with impaired insulin responsiveness.
Diabetes Care
PMID:Metformin and insulin receptors. 637 23

The postprandial blood glucose rise after a standard meal in six non-insulin dependent diabetics was significantly lower when acarbose 200 mg was taken together with the meal than without acarbose. Eight weeks acarbose treatment (300 mg), however, did not change fasting blood glucose. The effect of four weeks administration of the alpha-glucosidase inhibitor acarbose (300 mg) on diabetes regulation in another ten non-insulin dependent diabetics was compared with metformin (500 mg) in a double-blind cross-over study. Acarbose lowered postprandial blood glucose level from 11.5 +/- 4.2 to 8.9 +/- 1.8 mmol/l (p less than 0.02) and haemoglobin Alc from 8.1 +/- 1.8 to 7.7 +/- 1.7% (p less than 0.05). Urinary glucose was also decreased. Metformin did not significantly change postprandial blood glucose, haemoglobin A1c and urinary glucose excretion with the prescribed dose. The postprandial blood glucose and haemoglobin A1c after 4 weeks of treatment with acarbose and of metformin did not differ significantly. Side-effects of both drugs were mild and mainly gastrointestinal, but the frequency of side-effects was not different.
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PMID:Acarbose treatment of sulfonylurea-treated non-insulin dependent diabetics. A double-blind cross-over comparison of an alpha-glucosidase inhibitor with metformin. 639 73

A 62-year-old Indian with diabetic nephropathy controlled with metformin, developed miliary tuberculosis for which he was treated with rifampicin, isoniazid and ethambutol. Soon afterwards he developed cholestatic hepatitis and visual disturbance. Rifampicin and ethambutol were stopped. Streptomycin caused vertigo and had to be stopped. The introduction of para-aminosalicylic acid (PAS) led to hypoglycaemic coma. Metformin was stopped. Hypoglycaemic coma recurred. PAS was stopped and the patient's blood glucose concentrations became normal. Treatment with isoniazid and ethambutol led to total recovery from pulmonary tuberculosis. The induction of hypoglycaemia with PAS in this patient suggests a potential role for PAS in the treatment of diabetes mellitus.
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PMID:Para-aminosalicylic acid-induced hypoglycaemia in a patient with diabetic nephropathy. 739 95


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