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Biomedical subjects

A J Garber

Publications and source records attributed to A J Garber.

At least 73 records · Page 4Linked to original sources
PubMed1976

Alanine and glutamine synthesis and release from skeletal muscle. IV. beta-Adrenergic inhibition of amino acid release.

Alanine and glutamine formation and release were studied using the intact epitrochlaris preparation of rat skeletal muscle. Epinephrine reduced the release of alanine and glutamine in a concentration-dependent manner. Measurable inhibition was observed at 10(-9) M epinephrine, and maximal inhibition was obtained at 10(-5) M. Norepinephrine also reduced alanine and glutamine formation and release but the concentration required for maximal inhibition was approximately 100-fold greater than for epinephrine. Isoproterenol (beta agonist), but not phenylephrine (alpha agonist), reproduced the effects of epinephrine, and propranolol (beta antagonist), but not phentolamine (alpha antagonist), blocked the effect of the catecholamine. N6,O2'-Dibutyryl adenosine 3':5'-monophosphate reproduced the effects of epinephrine and theophylline potentiated the effect of submaximal concentrations of the hormone. Glucagon and prostaglandin E2 had no observable effect on amino acid release. Insulin did not modify the inhibition of alanine and glutamine release produced by epinephrine. Alanine and glutamine formation from added precursor amino acids was unaffected by epinephrine or cyclic adenosine 3':5'-monophosphate. Epinephrine reduced alanine formation in muscles obtained from diabetic rats or animals treated with thyroxine or cortisone. These findings indicate that physiological levels of catecholamines reduce alanine and glutamine formation and release from skeletal muscle. This effect is mediated by a beta-adrenergic receptor and the adenylate cyclase system and can be accounted for by an inhibition of muscle protein degradation.

Alanine↗
PubMed1976

The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man.

Sequential determinations of glucose outflow and inflow, and rates of gluconeogenesis from alanine, before, during and after insulin-induced hypoglycemia were obtained in relation to alterations in circulating epinephrine, norepinephrine, glucagon, cortisol, and growth hormone in six normal subjects. Insulin decreased the mean (+/-SEM) plasma glucose from 89+/-3 to 39+/-2 mg/dl 25 min after injection, but this decline ceased despite serum insulin levels of 153+/-22 mul/ml. Before insulin, glucose inflow and outflow were constant averaging 125.3+/-7.1 mg/kg per h. 15 min after insulin, mean glucose outflow increased threefold, but then decreased at 25 min, reaching a rate 15% less than the preinsulin rate. Glucose inflow decreased 80% 15 min after insulin, but increased at 25 min, reaching a maximum of twice the basal rate. Gluconeogenesis from alanine decreased 68% 15 min after insulin, but returned to preinsulin rates at 25 min, and remained constant for the next 25 min, after which it increased linearly. A fourfold increase in mean plasma epinephrine was found 20 min after insulin, with maximal levels 50 times basal. Plasma norepinephrine concentrations first increased significantly at 25 min after insulin, whereas significantly increased levels of cortisol and glucagon occurred at 30 min, and growth hormone at 40 min after insulin. Thus, insulin-induced hypoglycemia in man results from both a decrease in glucose production and an increase in glucose utilization. Accelerated glycogenolysis produced much of the initial, posthypoglycemic increment in glucose production. The contribution of glycogenolysis decreased with time, while that of gluconeogenesis from alanine increased. Of the hormones studied, only the increments in plasma catecholamines preceded or coincided with the measured increase in glucose production after hypoglycemia. It therefore seems probable that adrenergic mechanisms play a major role in the initiation of counter-regulatory responses to insulin-induced hypoglycemia in man.

Adrenergic alpha-Agonists↗
PubMed1974

Hepatic ketogenesis and gluconeogenesis in humans.

Splanchnic arterio-hepatic venous differences for a variety of substrates associated with carbohydrate and lipid metabolism were determined simultaneously with hepatic blood flow in five patients after 3 days of starvation. Despite the relative predominance of circulating beta-hydroxybutyrate, the splanchnic productions of both beta-hydroxybutyrate and acetoacetate were approximately equal, totaling 115 g/24 h. This rate of hepatic ketogenesis was as great as that noted previously after 5-6 wk of starvation. Since the degree of hyperketonemia was about threefold greater after 5-6 wk of starvation, it seems likely that the rate of ketone-body removal by peripheral tissues is as important in the development of the increased ketone-body concentrations observed after prolonged starvation as increased hepatic ketone-body production rate. Splanchnic glucose release in this study was 123 g/24 h, which was less than that noted previously after an overnight fast, but was considerably more than that noted during prolonged starvation. Hepatic gluconeogenesis was estimated to be 99 g/24 h, calculated as the sum of lactate, pyruvate, glycerol, and amino acid uptake. This was greater than that observed either after an overnight fast or after prolonged starvation. In addition, a direct relationship between the processes of hepatic ketogenesis and gluconeogenesis was observed.

Acetoacetates↗
PubMedDate not supplied

Magnesium utilization survey in selected patients with diabetes.

Patients with diabetes mellitus were surveyed to determine magnesium utilization and supplementation patterns and the extent to which these patterns correlate with American Diabetes Association (ADA) consensus panel recommendations. Participating ADA member physicians were asked to enroll five or more patients with insulin-dependent diabetes mellitus (IDDM, or type I diabetes) or non-insulin-dependent diabetes mellitus (NIDDM, or type II diabetes) who were not currently receiving magnesium supplementation and who they believed required or could benefit from oral magnesium chloride administration. Data were then collected regarding specific patient characteristics (ie, current diabetes therapy and glucose control); concomitant diseases and cardiovascular medications; baseline serum magnesium level, if measured before initiating magnesium chloride supplementation; and magnesium chloride dosage and duration. A total of 199 patients with diabetes began treatment with magnesium chloride supplementation after enrollment by a specialist. The mean baseline serum magnesium level for patients with IDDM was 1.48 mg/dL and for patients with NIDDM was 1.44 mg/dL (normal range, 1.80 to 2.40 mg/dL). No differences in mean serum magnesium levels were observed between men and women and between those with IDDM and those with NIDDM. Glucose control, as measured by glycosylated hemoglobin Alc, did not correlate with magnesium serum levels. A concomitant cardiovascular disease was present in 70% of patients. In 78.3% of patients, supplementation was initiated because of low serum magnesium levels; in 21.7%, magnesium chloride therapy was initiated empirically. No correlation was found between serum magnesium levels and the prescribed dosage or the recommended duration of magnesium therapy. Patterns of magnesium utilization among survey respondents generally followed ADA consensus panel recommendations. A majority of diabetic patients who were given magnesium chloride supplementation had concomitant cardiovascular disease. Primary care physicians and cardiologists who treat large numbers of patients with diabetes and cardiovascular disease should be knowledgeable of the ADA consensus report because of the high prevalence of hypomagnesemia and because of the consequences of magnesium deficiency in these high-risk groups. To achieve successful long-term maintenance in these patients, additional physician education appears to be necessary regarding initial dosing strategies and recommended duration of supplementation.

Diabetes Mellitus, Type 1↗
PubMedDate not supplied

Prevention and treatment of diabetic nephropathy: role of angiotensin-converting enzyme inhibitors.

OBJECTIVE: To discuss the role of angiotensin-converting enzyme inhibitors in the management of diabetes-related renal disease. METHODS: We review the published data from animal studies and clinical trials and outline the adverse effects that may limit the use of these drugs. RESULTS: Diabetic nephropathy is the most common cause of end-stage renal disease and dialysis in the United States. With improving measures to optimize blood glucose control and blood pressure, the progression from mild proteinuria to overt renal insufficiency can now be retarded or even arrested. Studies of therapeutic interventions have shown that angiotensin-converting enzyme inhibitors have a superior beneficial effect on nephropathy. Few adverse effects are associated with use of these drugs: a nonproductive cough is the most frequent side effect, and angioedema and agranulocytosis are the most serious (albeit rarely reported) effects. CONCLUSION: Angiotensin-converting enzyme inhibitors should be considered as first-line therapy for patients with diabetes who have microalbuminuria or macroalbuminuria.

Journal Article↗
PubMedDate not supplied

Dyslipidemia as a risk factor for coronary disease in patients with diabetes.

OBJECTIVE: To highlight the frequency of lipid abnormalities in patients with diabetes and the need for appropriate treatment strategies for coronary disease. METHODS: The epidemiologic features of coronary artery disease in the diabetic population are reviewed, and the pathogenesis of atherosclerotic disease is discussed. Various risk factors for predicting coronary artery disease and guidelines for therapeutic intervention are presented. RESULTS: The American Diabetes Association has estimated that 60% of all adults will die of coronary artery disease and that 80% of patients with diabetes will ultimately have atherosclerosis. The accelerated rate of atherosclerosis in patients with diabetes may be attributable to several factors, including hyperglycemia and insulin resistance. Abnormalities in lipid metabolism have a major role in the development of coronary disease. Because the National Cholesterol Education Program guidelines for treatment were established for less complicated hyperlipidemias, The American Diabetes Association recommends more aggressive lipid-lowering therapy at a lower level of low-density lipoproteins (130 mg/dL or 3.36 mmol/L) to produce an equivalent reduction in risk of coronary disease in patients with diabetes. CONCLUSION: In patients with diabetes, lipid levels should be aggressively reduced to decrease the possibility of coronary artery disease.

Journal Article↗
PubMedDate not supplied

Effect of premixed nph and regular insulin on glucose control and health-related quality of life in patients with type 2 diabetes mellitus.

OBJECTIVE: To compare the effect of the addition of regular insulin as a premixed 70/30 insulin to the treatment regimen of patients with type 2 diabetes who had used NPH insulin alone relative to overall glycemic control (postprandial blood glucose), patient satisfaction, and health-related quality of life. METHODS: We studied 90 patients with type 2 diabetes in a 10-week, randomized, double-blind, crossover trial involving 9 clinical investigators. Patients previously treated with NPH insulin alone were transferred to 30% regular insulin added to 70% NPH as a premixed insulin (70/30) administered twice daily. Patients in one sequence group received NPH insulin twice daily for 4 weeks followed by 70/30 insulin for 4 weeks; in the second sequence group, the order was reversed. RESULTS: The magnitude of the 1.5- and 2-hour postprandial glucose excursion was reduced with 70/30 insulin in comparison with NPH insulin, and patients treated with 70/30 insulin experienced fewer hypoglycemic events than with NPH insulin. With regard to health-related quality of life, patients treated with 70/30 insulin rated their physical functioning as better; rated their ability to be spontaneous, follow the meal plan, and interact socially to be less difficult; and had less fear of hypoglycemia and perceived their diabetes to be better controlled than when treated with NPH insulin alone. CONCLUSION: In patients with type 2 diabetes mellitus, premixed 70/30 insulin improved postprandial glycemic control and health-related quality of life without increasing the frequency of hypoglycemic events and without any additional cost.

Clinical Trial↗