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Biomedical subjects

A J Scheen

Publications and source records attributed to A J Scheen.

At least 343 records · Page 19Linked to original sources
PubMed1995

Amylin/islet amyloid polypeptide: biochemistry, physiology, patho-physiology.

Amylin is a 37 amino-acid peptide mainly produced by the islet beta-cell. Aggregation of amylin is partly responsible for amyloid formation. Amyloid deposits occur both extracellularly and intracellularly and may contribute to beta-cell degeneration. Amylin is packed in beta-cell granules and cosecreted with insulin in response to the same stimuli but, unlike other beta-cell products, it is produced from specific a gene on chromosome 12. Basal, plasma amylin concentrations are around 5 pM, and increase fourfold after meals or glucose. Higher levels are found in cases of insulin resistance, obesity, gestational diabetes and in some patients with NIDDM. Low or absent levels are found in insulin-dependent diabetic patients. There are similarities between amylin and non beta-cell peptides such as calcitonin gene related peptides (CGRP). They may bind to the same receptor, determine similar post-receptor phenomena and qualitatively similar actions but with different degree of potency. The actions of amylin are multiple and mostly exerted in the regulation of fuel metabolism. In muscle, amylin opposes glycogen synthesis, activates glycogenolysis and glycolysis (increasing lactate production). Consequently, amylin increases lactate output by muscle and increases the plasma lactate concentration. In fasting conditions, this lactate may serve as a gluconeogenic substrate for the liver, contributing to replenish depleted glycogen stores and to increase glucose production. In non-fasting conditions, lactate can be transformed by liver in triglycerides. It is not clear at present whether amylin actions on the liver are direct or mediated by changes in circulating metabolites. A probably indirect effect of amylin in muscle is to decrease insulin- (or glucose)-induced glucose uptake, which may contribute to insulin resistance. Other actions include inhibition of glucose-stimulated insulin secretion and, in general, actions mimicking CGRP effects. Some of these actions are seen at supraphysiological concentrations. The physiopathological consequences of amylin deficiency, or excess are under active by investigated.

Amino Acid Sequence↗
PubMed1995

Improving the action of insulin.

Improving the action of insulin is a relatively new concept in diabetes management. Insulin sensitivity can be improved by reduction of excessive body weight, regular physical activity and, possibly, by correcting a subclinical magnesium deficiency. Pharmacological means of improving insulin action include metformin, antiobesity serotoninergic agents and, possibly, benfluorex. New compounds aiming at improving the action of insulin are in development and include thiazolidinedione derivatives (known as "insulin sensitizers"), inhibitors of adipose tissue lipolysis (e.g. acipimox), and inhibitors of free fatty acid oxidation (e.g. etomoxir). Avoidance of drugs that reduce insulin sensitivity, such as beta blockers and thiazide diuretics, is recommended. Finally, cigarette smoking is associated with resistance to insulin but it remains to be demonstrated that cessation of cigarette smoking does in fact increase sensitivity to insulin.

Animals↗
PubMed1995

Glucose metabolism in obese subjects: lessons from OGTT, IVGTT and clamp studies.

Impaired glucose tolerance and overt diabetes are more frequent in presence than in absence of obesity. In obese subjects, glucose tolerance can be maintained within the normal range by compensating for insulin resistance by peripheral hyperinsulinism, the latter resulting from both increased insulin secretion and reduced insulin clearance. Impaired glucose tolerance is observed when insulin resistance is associated to impaired first-phase insulin response, which results in a significant increase in plasma glucose levels and a late insulin hyperresponsiveness. Both hyperinsulinaemia and hyperglycaemia are then able to overcome peripheral insulin resistance and impaired glucose disposal. When a more marked defect in insulin secretion is present, hyperglycaemia progresses, probably due to an additional participation of impaired suppression of hepatic glucose output. Overt diabetes then occurs with persistent post-absorptive hyperglycaemia. All these abnormalities can be reversed after a marked weight loss and recovery of ideal body weight, arguing for acquired rather than inherited metabolic defects in presence of morbid obesity. If a sufficient weight reduction can not be obtained, pharmacological approaches may be considered to improve insulin resistance of obese subjects, especially those with impaired glucose tolerance or overt diabetes.

Blood Glucose↗
PubMed1995

Retinopathy, but not neuropathy, is influenced by the level of residual endogenous insulin secretion in type 2 diabetes.

The files of 132 patients with Type 2 diabetes were retrospectively studied to characterize the influence of metabolic control and residual insulin secretion on neuropathy and retinopathy, the two most frequent degenerative diabetic complications. Patients were classified according to their metabolic control (mean HbA1C either < or > or = 8%; reference values: 3-6%) and residual endogenous insulin secretion (fasting plasma C-peptide levels either < or > or = 0.600 nmol/l). Neuropathy was more frequent in patients with poor metabolic control (32/64 = 50%) than in those adequately controlled (17/68 = 25%; p < 0.005). In both subgroups, the level of endogenous insulin secretion did not influence the prevalence of neuropathy. Retinopathy was less effected than neuropathy by the degree of metabolic control (37.5% in the subgroup with HbA1C > or = 8% v.s. 25% in the subgroup with HbA1C < 8%; p < 0.10), but was influenced by residual insulin secretion. Indeed, in patients with inadequate metabolic control, the prevalence of retinopathy was significantly increased in those with higher endogenous insulin secretion (51.4 versus 20.6%, p < 0.02) and thus probably higher insulin resistance. Furthermore, higher systolic arterial blood pressure was observed in the subgroups with a higher prevalence of retinopathy. Such conclusions were confirmed using multivariate analysis. Thus, in Type 2 diabetes, neuropathy is essentially affected by the degree of metabolic control, whereas retinopathy is also influenced by the level of residual endogenous insulin secretion and the presence of systolic hypertension.

Adult↗
PubMed1995

[How to explore insulin sensitivity in man?].

The two most widely used methods for studying insulin sensitivity in man are the euglycaemic hyperinsulinaemic clamp and the intravenous glucose tolerance test with minimal model assessment. The glucose clamp is the reference method, well validated and easy to interpret, which allows various extensions to the basic experimental procedure in order to obtain more valuable information on the specific effects of insulin on the various aspects of glucose metabolism. However, it is time-consuming and labour-intensive. In contrast, the intravenous glucose tolerance test is easier to perform, but its interpretation is much more difficult and requires a modeling approach called the "minimal model". If the intravenous glucose tolerance test probably represents a good screening test, mainly on a population basis, the glucose clamp still remains the gold standard method to study insulin sensitivity in man.

Female↗