Hemodynamic Effects Of Insulin Research Articles

Endothelin Limits Insulin Action in Obese/Insulin-Resistant Humans

The normal action of insulin to vasodilate and redistribute blood flow in support of skeletal muscle metabolism is impaired in insulin-resistant states. Increased endogenous endothelin contributes to endothelial dysfunction in obesity and diabetes. Here, we test the hypothesis that increased endogenous endothelin action also contributes to skeletal muscle insulin resistance via impairments in insulin-stimulated vasodilation. We studied nine lean and seven obese humans, measuring the metabolic and hemodynamic effects of insulin (300 mU . m(-2) . min(-1)) alone and during femoral artery infusion of BQ123 (an antagonist of type A endothelin receptors, 1 micromol/min). Endothelin antagonism augmented skeletal muscle responses to insulin in obese subjects through changes in both leg blood flow (LBF) and glucose extraction. Insulin-stimulated LBF was significantly increased in obese subjects only. These changes, combined with differential effects on glucose extraction, resulted in augmented insulin-stimulated leg glucose uptake in obese subjects (54.7 +/- 5.7 vs. 107.4 +/- 18.9 mg/min with BQ123), with no change in lean subjects (103.7 +/- 11.4 vs. 88.9 +/- 16.3, P = 0.04 comparing BQ123 across groups). BQ123 allowed augmented leg glucose extraction in obese subjects even in the face of NOS antagonism. These findings suggest that increased endogenous endothelin action contributes to insulin resistance in skeletal muscle of obese humans, likely through both vascular and tissue effects.

The Hemodynamic Effects of Insulin Following Overdosage with Levobupivacaine or Racemic Bupivacaine in Dogs

Although levobupivacaine (LBUP) is less cardiotoxic than racemic bupivacaine (RBUP), the resuscitation from the LBUP-induced cardiovascular collapse (CVC) has not been easy as expected. Following the recent reports that proposed the resuscitative action of insulin for the RBUP-induced CVC, a controlled trial was performed to assess the feasibility of insulin for the LBUP-induced CVC. Fourteen dogs were randomly allocated into two groups: the RBUP and LBUP groups. Each group received continuous intravenous infusions of RBUP or LBUP until the mean arterial pressure (MAP) reached 40 mmHg. Then, an intravenous bolus of insulin (2 U/kg) was administered. Both groups were successfully resuscitated. At CVC, a decrease of cardiac output and an increase of systemic vascular resistance were observed but to a lesser degree in the LBUP group (p<0.05). After insulin injection, the MAP further declined to under 40 mmHg for several minutes, which was more protracted in the LBUP group (p<0.05). The CVCs induced by LBUP or RBUP in anesthetized dogs could be successfully resuscitated by insulin. Compared with RBUP, however, the less degree of vasoconstriction by LBUP and the innate vasodilatory property of insulin yielded a delayed increment of MAP during the immediate resuscitation period in the LBUP-induced CVC.

Adaptation and maladaptation of the heart in diabetes: Part I: general concepts.

Diabetes mellitus (type 2 diabetes) is as much a disease of modern lifestyle as it is a disease of genetic predisposition. Worldwide, there are about 143 million patients with diabetes, almost 5 times more than estimates of 10 years ago.1,2⇓ Heart disease, often presenting as cardiomyopathy, is the leading cause of death among patients with diabetes mellitus (Figure 1).3 Like diabetes, the prevalence of heart failure also continues to rise in Western countries.4 Diabetes, in turn, is the largest comorbidity of patients with heart failure and adversely affects outcomes of cardiovascular disease.5 The trend is unmistakable; both insulin resistance and heart failure have emerged as major worldwide epidemics. It is therefore timely to take a fresh look at the effects of diabetes on the heart. Figure 1. Multiple Risk Factor Intervention Trial (MRFIT). Age-adjusted cardiovascular disease death rates (per 10 000 person-years) by presence of number of risk factors in men with and without diabetes. Reproduced with permission from Stamler et al.3 Copyright 1993 American Diabetes Association ( Diabetes Care . 1993;16:434–444). Reprinted with permission from the American Diabetes Association. The difficulties in making a causal connection between diabetes and heart failure are formidable. Some simple definitions remain elusive. For example, the distinction between the insulin-deficient (type 1) and insulin-resistant (type 2) forms of diabetes on the one hand, and the distinction between systolic and diastolic dysfunction as causes of heart failure, on the other hand, are hard to define. The known trophic and hemodynamic effects of insulin in healthy individuals,6 the well-described endothelial dysfunction, the deposition of advanced glycation end products, and an accelerated progression of atherosclerosis in patients with diabetes add further complexities to the clinical picture of heart failure in diabetes. Nonetheless, diabetes as a primary cause for heart failure …

The haemodynamic response to hyperinsulinaemia in hypertensive subjects.

In order to study if the vasodilatory action of insulin is impaired in essential hypertension, 24 untreated patients were challenged with a 2 h euglycaemic hyperinsulinaemic clamp (56 E/m2). Cardiac index (CI) was measured by thoracic impedance cardiography and leg blood flow (LBF) by Doppler ultrasound. During the clamp procedure a significant decline in blood pressure was seen (3.0-5.6% over 120 min, P < 0.001). However, no significant effects on ejection fraction (+6 +/- 8 s.d.%), CI (-1 +/- 2%), heart rate (+2 +/- 1%) or total peripheral resistance (TPRI, -0.5 +/- 2%) were found. LBF increased by 22 +/- 35% (P < 0.005). These haemodynamic effects of insulin were not related to age, sex, body mass index, blood pressure or the insulin-mediated glucose uptake during the clamp. In conclusion, insulin increased LBF, but no changes in CI and TPRI were seen in the hypertensive patients. Furthermore, no association between the ability of insulin to induce vasodilatation and to promote glucose uptake was seen.

Insulin stimulates epinephrine release under euglycemic conditions in humans

In healthy subjects, acute physiological hyperinsulinemia induces activation of the sympathetic nervous system, but in the absence of hypoglycemia, plasma epinephrine levels have not been found to increase during insulin administration. However, the venous level of epinephrine reflects the net result of release, clearance, and uptake and therefore is not a good measure of adrenomedullary epinephrine secretion. The influence of 90 minutes of euglycemic physiological hyperinsulinemia (60 mU · m −2 · min −1; plasma insulin concentration, ⋍700 pmol · L −1) on epinephrine kinetics using the 3H-epinephrine tracer method was studied in 12 healthy normotensive, non-obese subjects. After bolus injection, [ 3H]-epinephrine was continuously infused with arterial and venous blood sampling at regular intervals, enabling calculation of total body (systemic) and forearm epinephrine release and clearance. Studies were performed in the basal state and during sympathetic stimulation by lower-body negative pressure (LBNP) of − 15 mm Hg for 15 minutes. Control experiments (“sham” clamps, but with LBNP) were performed in four of the 12 individuals. Euglycemic hyperinsulinemia (all arterial glucose samples ≥ 4.2 mmol · L −1) induced an increase of the arterial epinephrine concentration ( P = .03), and tended to increase total body epinephrine release ( P = .08). Total body epinephrine clearance did not change during hyperinsulinemia. The insulin-induced increase in forearm blood flow ([FBF] by plethysmography, from 3.0 ± 0.4 to 3.8 ± 0.6 mL · dL −1 · min −1, P = .01) was strongly correlated with the increase in arterial epinephrine ( r = .78, P < .01). Plasma epinephrine concentrations did not change during control experiments (sham clamp). Sympathetic stimulation alone as induced by LBNP did not stimulate epinephrine release. However, the combination of insulin and LBNP significantly increased epinephrine release (from 0.37 ± 0.06 to 0.56 ± 0.12 nmol · m −1 · min −1, P = .03). We conclude that acute physiological hyperinsulinemia under euglycemic conditions induces epinephrine release. This effect is enhanced when hyperinsulinemia is combined with sympathetic stimulation by LBNP. Due to increased forearm removal, venous epinephrine concentrations hardly change. Epinephrine release was strongly correlated with the hemodynamic effects of insulin.

The Cardiac and Hemodynamic Effects of Insulin on Non-diabetic American Indians: The Strong Heart Study

The Cardiac and Hemodynamic Effects of Insulin on Non-diabetic American Indians: The Strong Heart Study

The cardiac and hemodynamic effects of insulin on non-diabetic American Indians: the strong heart study

The cardiac and hemodynamic effects of insulin on non-diabetic American Indians: the strong heart study

Mechanisms of altered hemodynamic and metabolic responses to insulin in patients with insulin-dependent diabetes mellitus and autonomic dysfunction.

Patients with autonomic neuropathy are more susceptible to insulin-induced hypotension than normal subjects, but the mechanisms are unclear. We quantitated the hemodynamic and metabolic effects of two doses of i.v. insulin (1 and 5 mU/kg.min, 120 min each) and several aspects of autonomic function in 28 patients with insulin-dependent diabetes mellitus (IDDM) and in 7 matched normal subjects under standardized normoglycemic conditions. The autonomic function tests included those predominantly assessing the integrity of vagal heart rate control (the expiration inspiration ratio during deep breathing and high frequency power of heart rate variability) and tests measuring sympathetic nervous function (reflex vasoconstriction to cold and blood pressure responses to standing and handgrip). During hyperinsulinemia, heart rate increased less (2 +/- 1 vs. 6 +/- 2 beats/min; P < 0.04) and diastolic blood pressure fell more (-3.1 +/- 1.2 vs. 0.9 +/- 2.1; P = NS) in the patients with IDDM than in the normal subjects. Forearm vascular resistance decreased significantly in the patients with IDDM [by -7.1 +/- 1.4 mm Hg/(mL/dL.min); P < 0.001 for high vs. low dose insulin], but not in the normal subjects (-0.1 +/- 2.5 mm Hg/(mL/dL.min; P = NS). Reflex vasoconstriction to cold was inversely correlated with the decreases in diastolic (r = -0.51; P < 0.005) and systolic (r = -0.59; P < 0.001) blood pressure and forearm vascular resistance (r = -0.53; P < 0.005), but not with the change in heart rate. The expiration inspiration ratio was, however, directly correlated with the insulin-induced change in heart rate (r = 0.63; P < 0.001), but not with diastolic or systolic blood pressure or forearm vascular resistance. Whole body (48 +/- 2 vs. 67 +/- 5 mumol/kg.min; P < 0.005) and forearm (44 +/- 4 vs. 67 +/- 8 mumol/kg.min; P < 0.05) glucose uptake were significantly lower in the IDDM patients than in the normal subjects. The latter could be attributed to a defect in the forearm glucose arterio-venous difference (1.5 +/- 0.1 vs. 2.2 +/- 0.2 mmol/L, respectively; P < 0.01), but not in blood flow. We conclude that both impaired vagal heart rate control and sympathetic nervous dysfunction exaggerate the hemodynamic effects of insulin in patients with IDDM and could contribute to insulin-induced hypotension.

Renal and ocular hemodynamic effects of insulin

Renal and ocular hemodynamic effects of insulin

Metabolic and hemodynamic effects of insulin on human hearts.

Myocardial muscle is considered to be a target tissue for insulin action, but direct measurements of insulin's effects on cardiac hemodynamics and intermediary metabolism in humans are scarce. We combined great cardiac vein (GCV)/arterial catheterization with the euglycemic insulin clamp technique and thermodilution in six healthy middle-aged (53 +/- 2 yr) volunteers. In the fasting state, the myocardium extracted free fatty acid (FFA), lactate, pyruvate, glycerol, and beta-hydroxybutyrate (6.4 +/- 0.8, 6.2 +/- 1.0, 0.58 +/- 0.12, 0.44 +/- 0.15, and 11 +/- 2 mumol/min, respectively) and consumed 0.26 +/- 0.02 mmol/min oxygen. As fasting plasma insulin (73 +/- 6 pmol/l) was raised and clamped at 503 +/- 16 pmol/l for 100 min while maintaining euglycemia (approximately 5 mmol/l), arterial levels of lactate and pyruvate rose (by 121 and 159%, respectively), whereas FFA, glycerol, and beta-hydroxybutyrate fell (by 69, 48, and 85%, respectively, all P < 0.001). Correspondingly, net myocardial uptake of glucose, lactate, and pyruvate increased to 18.9 +/- 3.5, 32.0 +/- 2.3, and 2.7 +/- 0.5 mumol/min, respectively, whereas net extraction of circulating FFA, glycerol, and beta-hydroxybutyrate was abolished (all P < 0.001). The stimulation of lactate and pyruvate uptake was the result of both increased arterial supply and enhanced myocardial extraction ratio (from 19 +/- 3 to 51 +/- 6% for lactate, from 26 +/- 5 to 44 +/- 5% for pyruvate, P < 0.001 for both). This shift from fat to carbohydrate fuel usage occurred in the absence of changes in oxygen consumption, heart rate, GCV blood flow, aortic pressures, coronary vascular resistance, and left ventricular end-diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac metabolic and hemodynamic effects of insulin in patients with coronary artery disease

Cardiac metabolic and hemodynamic effects of insulin in patients with coronary artery disease

Haemodynamic effects of insulin and beta receptor blockade during acute left ventricular failure in dogs.

Acute ischaemic heart failure was induced in 13 dogs by coronary embolisation. Severe dysfunction of the left ventricular (LV) performance was shown by a significant increase in LV end-diastolic pressure and significant decreases in maximum rate of LV pressure rise (LVdP/dtmax), stroke volume and cardiac output. 300 IU of fast-acting insulin was injected as a bolus dose in 7 dogs 90 min after the embolisation procedure. This was followed by infusion of glucose and potassium to maintain normal blood levels. After 15 min, insulin had significantly improved the performance of the failing left ventricle. Total peripheral resistance was decreased. Myocardial blood flow was significantly increased while myocardial oxygen consumption was unchanged. After beta receptor blockade with propranolol 0.5 mg kg-1 given intravenously, the improvement in cardiac performance was reduced, heart rate decreased, and a concomitant decrease in myocardial blood flow and oxygen consumption was recorded. Compared with values before treatment, the net effect of combined insulin and beta receptor blockade was unchanged LVdP/dtmax, LV end-diastolic pressure and cardiac output, significantly increased stroke volume and decreased heart rate, and moderately reduced total peripheral resistance and mean aortic blood pressure. Myocardial blood flow was unaltered, while myocardial oxygen consumption was significantly reduced. In the control group of 6 dogs propranolol was given before insulin, and similar haemodynamic alterations were found.