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Biomedical subjects

C Berne

Publications and source records attributed to C Berne.

At least 127 records · Page 7Linked to original sources
PubMed1990

The cytoplasmic Ca2+ response to glucose as an indicator of impairment of the pancreatic beta-cell function.

The effects of glucose on the cytoplasmic Ca2+ concentration (Ca2+i) regulating insulin release were investigated using pancreatic beta-cells representative for the normal and diabetic situations. Increase of the glucose concentration resulted in a slight lowering of Ca2+i followed by a rise, often manifested as high amplitude oscillations. The Ca2+i-lowering component in the glucose action associated with suppression of insulin release became particularly prominent when the beta-cells were already depolarized by tolbutamide. Glucose-induced inhibition of insulin release was observed also in experiments with rats made diabetic with streptozotocin or alloxan. Other studies indicated lowering of plasma insulin after intravenous glucose administration in patients with insulin- and noninsulin-dependent diabetes mellitus. Brief exposure of beta-cells to 2.2 mmol l-1 streptozotocin resulted in impairment of the response to glucose, manifested as disappearance of the cyclic variation of Ca2+i. The results indicate that glucose-induced depolarisation is a vulnerable process, the disturbance of which may contribute to insulin secretory defects in diabetes mellitus.

Animals↗
PubMed1990

Lack of cutaneous hyperemia in response to insulin-induced hypoglycemia in IDDM.

Cutaneous blood flow was measured with the laser Doppler technique and by recording cutaneous O2 tension on the forearm and forehead in nine young adult patients with insulin-dependent diabetes mellitus (IDDM) and nine sex- and age-matched healthy control subjects after induction of hypoglycemia. In the healthy subjects, cutaneous blood flow measured with the laser Doppler technique was increased by 120 +/- 26% in the forehead (P less than 0.01) and 196 +/- 50% in the forearm (P less than 0.01) at the glucose nadir (blood glucose 1.8 +/- 0.2 mM) compared with basal blood flow. In contrast, in diabetic patients, cutaneous blood flow was unchanged. The corresponding changes, at the glucose nadir, with cutaneous O2 tension recordings were 286 +/- 131% (P less than 0.05) in control subjects and -22 +/- 15% (NS) in diabetic patients. An impairment of sympathetic nervous function, not detectable by simple cardiovascular tests, could be responsible for the lack of cutaneous hyperemia and sweating and could contribute to unawareness of hypoglycemia in diabetic patients.

Adult↗
PubMed1990

Insulin sensitivity in newly detected hypertensive patients: influence of captopril and other antihypertensive agents on insulin sensitivity and related biological parameters.

In a recent study in which metabolic characteristics of newly detected obese and nonobese hypertensive subjects were compared with those of normotensive subjects, insulin sensitivity was decreased, fasting insulin values and insulin values after an intravenous glucose tolerance test (IVGTT) were increased, and fasting and IVGTT glucose values were increased in both hypertensive groups. Furthermore, adverse alterations in lipid profile variables were found in the hypertensive groups when compared with the normotensive group. The effects of various antihypertensive agents on these metabolic variables have been assessed in prospective trials. Treatment with the beta 1-selective blocking agents metoprolol and atenolol was associated with decreased insulin sensitivity and increased fasting values of insulin and glucose. There were also indications of a suppressive effect on insulin secretion during IVGTT, as well as an increase in serum triglycerides and a decrease in serum high-density lipoprotein cholesterol. Hydrochlorothiazide treatment was associated with a decrease in insulin sensitivity and an increase in blood glucose concentrations. In addition, hydrochlorothiazide increased total cholesterol, particularly the low-density lipoprotein fraction. The calcium channel blocker diltiazem did not appear to produce any negative metabolic effects. Treatment with the angiotensin converting enzyme inhibitor captopril resulted in increased insulin sensitivity with no adverse effects on lipids. All of the agents reduced blood pressure to a similar degree. These findings, and those of other studies, suggest that captopril and diltiazem offer advantages over the other agents with regard to effects on risk factors for coronary artery disease other than hypertension. Unlike diltiazem, captopril improves insulin sensitivity and this may prove to be important.

Antihypertensive Agents↗
PubMed1989

A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension.

It has been suggested that the metabolic side effects of antihypertensive drugs are responsible for their failure to reduce cardiovascular morbidity in patients with hypertension. Therefore, in 50 patients with essential hypertension, we performed a randomized, double-blind, crossover study comparing the effects of carbohydrate and lipid metabolism of captopril (mean [+/- SD] dose, 81 +/- 24 mg per day) and hydrochlorothiazide (40 +/- 12 mg per day) over two four-month treatment periods. Captopril increased the insulin-mediated disposal of glucose, as compared with placebo, from 5.7 +/- 2.4 to 6.3 +/- 2.5 mg per kilogram of body weight per minute (P less than 0.05), whereas hydrochlorothiazide caused a decrease from 6.4 +/- 2.0 to 5.7 +/- 1.9 (P less than 0.01). Captopril had no effect on the basal insulin concentration, but it decreased the late (30- to 90-minute) insulin response to glucose and increased the early (2- to 6-minute) insulin peak. Hydrochlorothiazide increased the basal insulin concentration and the late insulin response to glucose. These findings may be explained by an increase in insulin sensitivity with captopril and a decrease with hydrochlorothiazide. Little or no change was seen in serum lipid or lipoprotein levels during treatment with captopril, whereas hydrochlorothiazide caused significant increases in serum total (5 percent) and low-density lipoprotein (6 percent) cholesterol levels and total (15 percent) and very-low-density lipoprotein (25 percent) triglyceride levels, as compared with placebo (P less than 0.01 for all comparisons). We conclude that hydrochlorothiazide for the treatment of essential hypertension has adverse effects on glucose and lipid metabolism. It is possible, but not proved in this study, that these changes may contribute to the risk for diabetes mellitus and coronary heart disease. In contrast, captopril appears to have beneficial or no effects on glucose and lipid metabolism.

Blood Glucose↗
PubMed1989

Sensitivity to insulin during treatment with atenolol and metoprolol: a randomised, double blind study of effects on carbohydrate and lipoprotein metabolism in hypertensive patients.

OBJECTIVE: To compare the effects of metoprolol and atenolol on carbohydrate and lipid metabolism and on insulin response to an intravenous glucose load. DESIGN: Randomised, double blind, double dummy, controlled crossover trial. SETTING: University Hospital, Uppsala, Sweden. PATIENTS: 60 Patients with primary hypertension (diastolic blood pressure when resting supine 95-119 mm Hg on at least two occasions during four to six weeks of treatment with placebo) randomised to receive either metoprolol (n = 30) or atenolol (n = 30) during the first treatment period. INTERVENTIONS: Placebo was given for a run in period of four to six weeks. Metoprolol 100 mg twice daily or atenolol 25 mg twice daily was then given for 16 weeks. The two drugs were then exchanged and treatment continued for a further 16 weeks. END POINT: Evaluation of effects of treatment with metoprolol and atenolol on glucose, insulin, and lipid metabolism and glucose disposal mediated by insulin. MEASUREMENTS AND MAIN RESULTS: Reduction of blood pressure was similar and satisfactory during treatment with both drugs. Glucose uptake mediated by insulin was measured during a euglycaemic hyperinsulinaemic clamp to evaluate patients' sensitivity to insulin. Glucose uptake decreased from 5.6 to 4.5 mg/kg/min when patients were taking metoprolol and from 5.6 to 4.9 mg/kg/min when they were taking atenolol. Both drugs caused a small increase in fasting plasma insulin and blood glucose concentrations and glycated haemoglobin concentration. Despite decreased sensitivity to insulin the increase in insulin concentration in response to an intravenous glucose tolerance test was small, suggesting inhibition of release of insulin. Very low density lipoprotein and low density lipoprotein triglyceride concentrations were increased with both drugs and high density lipoprotein cholesterol concentration was decreased. Low density lipoprotein cholesterol concentration was not affected. CONCLUSIONS: Long term use of metoprolol and atenolol causes metabolic abnormalities that may be related to the increased incidence of diabetes in patients with hypertension who are treated pharmacologically. These results may help to explain why the two drugs have failed consistently to reduce the incidence of coronary heart disease in several large scale studies.

Atenolol↗
PubMed1989

Changes of sympathetic nerve activity induced by 2-deoxy-D-glucose infusion in humans.

Microelectrode recording of sympathetic signals in the peroneal nerve was performed in 14 healthy volunteers following infusion of 2-deoxy-D-glucose (50 ml/kg body wt). Heart rate, blood pressure, body temperature, hematocrit, and blood levels of glucose, insulin, and catecholamines were monitored. Muscle nerve sympathetic activity (MSA), which is involved in cardiovascular homeostasis, increased significantly from a base-line level of 19.9 +/- 4.5 (mean +/- SE) bursts/min to a peak 30 min after the start of the infusion of 33.1 +/- 5.1 bursts/min. Skin nerve sympathetic activity (SSA), which is a mixture of sudomotor and vasoconstrictor signals, also increased to a peak at 30 min. The impulse pattern of SSA suggested that the increase involved mainly sudomotor activity, with simultaneous inhibition of vasoconstrictor signals. The time courses of MSA and the circulatory responses suggested that the increase in MSA was not a baroreceptor-induced counteraction of the cardiovascular changes during glucopenia. The responses of MSA and SSA were remarkably similar to those observed previously during insulin-induced hypoglycemia. The relationship between changes of sympathetic outflow, glucose levels, and insulin levels in the present study indicates that the effects observed are consequences of central nervous system glucopenia, with insulin playing a minor role. It is concluded that the sympathoadrenal system responds in a markedly differentiated way to glucopenia.

Adult↗
PubMed1989

Sympathetic response to oral carbohydrate administration. Evidence from microelectrode nerve recordings.

Microneurography was used to measure sympathetic outflow in human muscle nerves (MSA) for up to 90 min after the ingestion of 100 g D-glucose, 75.8 g D-xylose, intravenous D-glucose (0.35 g/kg), and 300 ml water. 19 healthy subjects were examined using a microelectrode positioned in the right peroneal nerve. MSA increased from 21 +/- 0.9 bursts/min at rest to 36.9 +/- 4.3 bursts/min 30 min after ingestion of D-glucose and from 18.9 +/- 2.9 to 26.3 +/- 3.4 bursts/min 30 min after D-xylose. The increase in MSA was already significant by 15 min. MSA had not returned to the basal level after 90 min. Neither intravenous D-glucose nor water intake enhanced MSA. MSA increased in parallel with plasma norepinephrine, and a significant correlation (r = 0.55; P less than 0.001) was observed between the plasma insulin concentration and MSA after D-glucose ingestion. In three subjects the outflow of sympathetic nerve activity to the skin was examined after oral D-glucose and no change was observed, emphasizing the differentiated nature of the sympathetic nerve response to carbohydrate. Multiple factors such as insulin alone, hemodynamic adjustment to splanchnic vasodilation, and gastrointestinal distension are probably involved in the increased muscle nerve sympathetic outflow after carbohydrate ingestion.

Adult↗
PubMed1989

Plasma volume substitution does not inhibit plasma noradrenaline and muscle nerve sympathetic responses to insulin-induced hypoglycaemia in healthy humans.

Microelectrode recordings of muscle nerve sympathetic activity and measurements of venous plasma noradrenaline have indicated increased sympathetic outflow during acute hypoglycaemia. Plasma volume reduction during hypoglycaemia, as evidenced by increasing peripheral venous haematocrit might underly the sympathetic activation. To study the effect of prevention of plasma volume reduction during hypoglycaemia, saline containing albumin was infused intravenously in healthy adult volunteers during hypoglycaemia. Hypoglycaemia was induced by an intravenous injection of soluble insulin in a dose of 0.15 IU/kg body weight. Peripheral venous plasma noradrenaline concentrations were identical in experiments without and with plasma volume substitution. Muscle nerve sympathetic activity increased to the same extent during hypoglycaemia with and without plasma volume substitution. It is concluded that increased plasma noradrenaline concentrations and enhanced muscle nerve sympathetic activity during insulin-induced hypoglycaemia in man are not consequences of plasma volume reduction.

Adult↗
PubMed1989

C-peptide but not insulin concentrations are related to the serum lipoprotein levels during insulin treatment of non-insulin-dependent diabetes mellitus (NIDDM) patients.

In 21 non-insulin-dependent diabetic patients with secondary drug failure, once-daily long-acting insulin lead to a moderately improved metabolic control. At the conclusion of the study (eight months) the fasting blood glucose and HbA1c concentrations were significantly decreased, but the postprandial blood glucose concentrations in the afternoon were unaltered. The peripheral insulin sensitivity, as measured by the intravenous insulin tolerance test, and the lipoprotein lipase activity in adipose and skeletal muscle tissue had increased. After initiation of insulin therapy there was a transient decrease of the fasting and glucagon-stimulated C-peptide concentrations. The very low density lipoprotein lipids and apolipoprotein B, A-I and A-II were also reduced transiently. The only significant difference in lipoprotein composition at eight months compared with on admission, was an increased cholesterol and decreased triglyceride concentration in the high density lipoproteins. There were significant relationships between the C-peptide, but not the peripheral insulin, concentrations and the serum lipid concentrations. This may indicate that high peripheral insulin concentrations after administration of exogenous insulin may affect the hepatic lipoprotein production less than the portal insulin concentrations mainly derived from endogenous production.

Biomarkers↗
PubMed1988

Application of prazosin is associated with an increase of insulin sensitivity in obese patients with hypertension.

The aim of this study was to determine whether insulin sensitivity measured by the euglycaemic insulin clamp technique is lower in patients with primary hypertension than in matched healthy control subjects, and whether this sensitivity was affected after 12 weeks of antihypertensive treatment with the alpha 1-adrenoceptor blocking drug prazosin. Twelve moderately obese normoglycaemic patients (four men), with hypertension not previously treated with pharmacological agents and diastolic blood pressure above 100 mm Hg, and 12 healthy matched control subjects participated. Supine blood pressure decreased 12/5 mm Hg (p less than 0.01) and standing blood pressure 14/9 mm Hg (p = 0.001) during prazosin treatment (mean dosage 5.3 +/- 1.6 mg/day (SD]. During euglycaemic insulin clamp studies the control subjects showed a higher mean glucose uptake than the untreated hypertensive patients (7.5 +/- 1.0 and 5.8 +/- 1.9 mg.kg b.w.-1.min-1, respectively, p less than 0.01). During prazosin treatment there was no significant difference between the hypertensive patients and the control subjects in this respect (6.6 +/- 2.8 and 7.5 +/- 1.0, respectively, p = 0.21). During prazosin treatment, however, the disappearance rate of glucose decreased during the intravenous glucose tolerance test (from 1.7 +/- 0.9 to 1.3 +/- 0.6, p less than 0.02) and the area under the glucose concentration-time curve decreased by 38% (from 473 +/- 119 to 294 +/- 99, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗