Glucose homeostasis is partly due to the metabolic action of insulin, which exerts its antihyperglycaemic action mainly in liver, adipose tissue and skeletal muscle. In the basal state, skeletal muscle utilizes little glucose as a fuel for its own needs [1]. In contrast, during postprandial periods the disposal of glucose is partly insulin-mediated and occurs mainly in skeletal muscle [2], where it is largely stored as glycogen. At this time, skeletal muscle switches from a low glucose-consuming to a major carbohydrate-utilizing system. Glucose uptake is increased by the combined effects of the prevailing serum glucose concentration (mass action effect) and by endogenous insulin elevation which stimulates glucose extraction by recruiting and activating specific transporters.In addition to the metabolic and nervous factors, blood flow might be another parameter regulating glycaemia. Under normal daily physiological conditions, plasma levels of glucose and insulin vary considerably, in particular during repeated postprandial periods. If these substances exert vasoactive effects, they may consequently play a prominent role in the optimal regulation of glucose homeostasis [3,4]. Several studies have reported that, in addition to its met- Diabetologia (1998) 41: 26--33 Hyperglycaemia modifies the reaction of microvessels to insulin in rat skeletal muscle Summary The role played by glucose and/or insulin in local vascular regulation of tissue glucose uptake is largely unknown. Thus, the aim of this study was to examine microvascular changes induced either by hyperinsulinaemia alone or in combination with hyperglycaemia. The effects of insulin or glucose on the diameter and periodic vasomotion of precapillary arterioles (diameter < 20 mm) were determined by using the spinotrapezius muscle preparation in fasted, anaesthetized rats. Ten minutes after s. c. insulin administration, the blood insulin level was greatly increased whereas plasma glucose remained unchanged. This was associated with a marked and durable vasodilation of terminal arterioles without significant changes in vasomotion. When similar plasma insulin levels were attained by glucose infusion, tissue glucose uptake was increased in spite of a partial constriction and increased vasomotion of precapillary arterioles. Importantly, local tissue blood flow was not reduced despite the diminution in microvascular diameters. These results indicate that hyperinsulinaemia alone produces an increase in the diameter of terminal arterioles. This effect seems to be offset when the same level of hyperinsulinaemia is associated with hyperglycaemia (such as occurs postprandially), as illustrated by vasoconstriction of the muscle terminal arterioles. Our data suggest that the vasoconstriction of precapillary arterioles may be part of an active regulation for optimal glucose supply to the tissue in acute hyperglycaemic episodes. These data provide the first direct evidence that insulin and glucose can act as regulators of microflow in the skeletal muscle, as illustrated b...
Aims/hypothesis. In vitro studies have suggested that glycation of LDL might be implicated in diabetic microangiopathy. We therefore investigated the in vivo effects of LDL glycated in vitro on the mouse skeletal muscle arteriolar tone. Since glycation naturally occurs during diabetes, we also tested the effects of LDL isolated from diabetic patients. Methods. In anaesthetized mice, the spinotrapezius muscle microcirculation was observed, in situ, using the orthogonal polarization spectral imaging technology. The diameter of terminal (<20 µm) and small arterioles (20-40 µm) was measured before and after a bolus intravenous injection of glycated LDL followed by a continuous perfusion (115 µg/kg/min). Results. A slight decrease of terminal and small arterioles diameter (<10%) was observed with native LDL and LDL isolated from healthy subjects. In contrast, mildly glycated LDL induced a clear vasoconstriction of arterioles (>15%), which was further increased when highly glycated LDL was perfused (>22%). LDL isolated from diabetic patients mimicked the vasoconstriction obtained with in vitro mildly glycated LDL, which underwent similar glycation as those isolated from diabetic patients. Conclusion/Interpretation. Our results show in vivo that acute perfusion of both types of glycated LDL (artificially or naturally modified), cause major microvascular modification by enhancing arteriolar tone in skeletal muscle. These findings highlight a new role of glycated LDL at the level of microvessels. We suggest that glycation of LDL could contribute to the impaired vascular reactivity observed in diabetes. [Diabetologia (2003[Diabetologia ( ) 46:1550[Diabetologia ( -1558
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