Abnormalities of glucose metabolism in spontaneously hypertensive rats

Abnormalities in glucose metabolism and insulin action are frequently detected in patients with essential hypertension. Spontaneously hypertensive rats (SHR) have been used as an experimental model to understand this pathological condition. The objective of the present study was to assess glucose metabolism and insulin action in SHR and Wistar rats under fed and fasting conditions. Peripheral glucose utilization was estimated by kinetic studies with [6-3H]-glucose and gluconeogenetic activity was measured during continuous [14C]-bicarbonate infusion. Plasma glucose levels were higher in the SHR group. Plasma insulin levels in the fed state were higher in the SHR group (99.8 +/- 6.5 ÁM) than in the control group (70.4 +/- 3.6 ÁM). Muscle glycogen content was reduced in SHR compared to control under the various experimental conditions. Peripheral glucose utilization was slightly lower in the SHR group in the fed state (8.72 +/- 0.55 vs 9.52 +/- 0.80 mg kg-1 min-1 in controls). Serum free fatty acid levels, hepatic glycogen levels, hepatic phosphoenolpyruvate carboxykinase activity and gluconeogenetic activity were similar in the two groups. The presence of hyperglycemia and hyperinsulinemia and the slightly reduced peripheral glucose utilization suggest the presence of resistance to the action of insulin in peripheral tissues of SHR. Hepatic gluconeogenesis does not seem to contribute to the metabolic alterations detected in these animals

Role of bradykinin in postprandial hypotension in humans

A transient significant decrease in mean arterial blood pressure (MAP) from 107 + ou - 3 to 98 + ou - 3 mmHg (P<0.05) was observed in elderly (59-69 years of age), healthy volunteers 25-30 min following ingestion of a test meal. In young volunteers (22-34 years of age), a postprandial decrease of MAP from 88 + ou - 3 to 83 + ou - 4 mmHg was also noted but it was not statistically significant. A 40 per cent decrease in bradykinin (BK) content of circulatory high molecular weight kininogen had previously been observed in human subjects given the same test meal. We presently demonstrate by specific ELISA that the stable pentapeptide metabolite (1-5 BK) of BK increases from 2.5 + ou - 1.0 to 11.0 + ou - 2.5 pg/ml plasma (P<0.05) in elderly volunteers and from 2.0 + ou - 1.0 to 10.3 + ou - 3.2 pg/ml plasma (P<0.05) in young volunteers 3 h following food intake. This result suggests that ingestion of food stimulates BK release from kininogen in normal man. Postprandial splanchnic vasodilatation, demonstrated by a decrease of plasma half-life of intravenously administered indocyanine green (ICG), a marker of mesenteric blood flow to the liver, from 4.4 + ou - 0.4 to 3.0 + ou - 0.1 min (P<0.05) in young volunteers and from 5.2 + ou - 1.0 to 4.0 + ou - 0.5 min (P<0.05) in elderly volunteers, accompanied BK release. The participation of BK in this response was investigated in subjects given the BK-potentiating drug captopril prior to food intake. Postprandial decreases of ICG half-lives were not changed by this treatment in either young or elderly subjects, a result which may indicate that BK released following food intake plays no role in postprandial splanchnic vasodilatation in normal man.

Peripheral glucose metabolism in patients with chronic renal failure

The present study was designed to determine the effect of chronic renal failure on forearm muscle glucose uptake and oxidation during the postabsorptive state and after an oral glucose challenge. Twelve normal subjects and sixteen patients with chronic renal failure were studied after an overnight fast (12-14h) and for 3h after the ingestion of 75g glucose. Peripheral glucose metabolism was analyzed by the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry. decreased forearm glucose uptake was observed in uremic patients compared to normal subjects (9l.5 ñ 11,4 vs 154.8 ñ 7.8mg 100 ml forearm -1 3h-1) with diminished nonoxidative glucose metabolism (69.4 ñ 12.1 vs 117.2 ñ 12.8mg 100 ml forearm-1 3h-1). Muscle glucose oxidation did not difer significantly between groups. Both serum free fatty acid levels and lipid oxidation rates were similar in the normal subjects and the uremic patients, and declined in a similar fashion after glucose ingestion. Basal serum insulin levels did not differ significantly between normal and uremic patients, whereas the insulinemic response to glucose load was greater among the patients with chronic renal failure. These data show that resistance occurring in patients with chronic renal failure is accompanied by impaired muscle glucose uptake and nonoxidative glucose metabolism