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Biomedical subjects

J E Gerich

Publications and source records attributed to J E Gerich.

At least 127 records · Page 7Linked to original sources
PubMed1984

Effects of epinephrine infusion on leucine and alanine kinetics in humans.

Infusion of epinephrine in humans increases glucose production and decreases plasma concentrations of some essential amino acids such as leucine, while not affecting the plasma concentration of the potential gluconeogenic amino acid alanine. To determine whether epinephrine alters alanine and leucine metabolism, rates of appearance (Ra) and disappearance (Rd) of glucose, alanine, and leucine were determined in postabsorptive volunteers using [3H]glucose, [2H3]alanine, [15N]leucine, and [2H3]leucine during a 180-min infusion of epinephrine (50 ng X kg-1 X min-1). Plasma glucose (90 +/- 1 to 142 +/- 5 mg/dl) and insulin (10 +/- 1 to 16 +/- 2 micrograms/ml) increased (P less than 0.05), whereas plasma alanine concentrations did not change and plasma leucine concentrations increased (127 +/- 5 to 72 +/- 3 microM). Glucose Ra increased transiently and returned to basal values by 120 min. In contrast, alanine Ra and Rd increased identically and progressively from 5.7 +/- 0.5 to 14.5 +/- 1.9 mumol X kg-1 X min-1 by 180 min. Although leucine nitrogen Ra increased transiently and returned to basal values, leucine carbon Ra and Rd decreased (P less than 0.05) during the infusion of epinephrine. The calculated rate and percent of leucine nitrogen going to alanine increased, whereas the percent of alanine nitrogen derived from leucine remained constant. The increase in alanine Ra was entirely attributable to increased de novo synthesis because proteolysis, as estimated by leucine carbon flux, decreased.

Adolescent↗
PubMed1984

Glucose counterregulation during prolonged hypoglycemia in normal humans.

To study glucose counterregulation under conditions approximating those of clinical disorders in which hypoglycemia develops gradually and is reversed over a prolonged period, we injected regular insulin subcutaneously, in a dose (0.15 U/kg) selected to produce two- to threefold increases in plasma insulin, in 11 normal human volunteers and measured plasma glucose, insulin, C-peptide, and counterregulatory hormone concentrations as well as rates of glucose production, glucose utilization, and insulin secretion over 12 h. The data suggest that the mechanisms of gradual recovery from prolonged hypoglycemia may differ from those of rapid recovery from short-term hypoglycemia produced by intravenous injection of insulin in that 1) both stimulation of glucose production and limitation of glucose utilization contribute to recovery from prolonged hypoglycemia; 2) increases in glucagon, epinephrine, growth hormone, and cortisol secretion as well as a decrease in insulin secretion may all participate in glucose counterregulation during prolonged hypoglycemia; 3) epinephrine may play a more important role than glucagon during prolonged hypoglycemia. The latter two conclusions are based primarily on the temporal relationships between changes in the rates of glucose turnover and changes in plasma hormone concentrations and should not be considered proved. However, they provide the basis for testable hypotheses concerning the physiology of gradual recovery from prolonged hypoglycemia that can be expected to be relevant to the pathophysiology of clinical hypoglycemia.

Adult↗
PubMed1984

Increased leucine flux in short-term fasted human subjects: evidence for increased proteolysis.

Plasma leucine concentration increases with short-term fasting in normal humans. In previous studies using an 18-h constant infusion of [2H3]leucine, a 15% decrease in the rate of appearance (Ra) of leucine was observed between 15 and 30 h of fasting. However, incorporation of labeled leucine into and subsequent release from body protein could result in an apparent decrease in leucine Ra. The present studies were undertaken to determine the rate of leucine N and carbon flux in short-term fasted human subjects in using an experimental design that would minimize potential recycling of label. Six normal subjects were infused with [15N]- and [2H3]leucine for two 4-h periods (0600 to 1000 h and 2000 to 2400 h) during a 30-h fast. Between the 15th and 30th h of fasting, plasma leucine concentration (102 +/- 10 to 169 +/- 18 microM, P less than 0.01) and leucine C (1.46 +/- 0.05 to 1.64 +/- 0.10 mumol X kg-1 X min-1, P less than 0.05) and leucine N (1.93 +/- 0.14 to 2.49 +/- 0.26 mumol X kg-1 X min-1, P less than 0.05) flux increased, whereas the metabolic clearance rates of leucine C and N decreased (P less than 0.01 and less than 0.05, respectively). Therefore, when isotope recycling is minimized with short periods of isotope infusion, leucine flux increases between 15 and 30 h of fasting. Because the only source of leucine in the postabsorptive periods is body protein, we conclude that the rate of whole-body proteolysis is increased in short-term fasting in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Glucose production and utilization in children with glycogen storage disease type I.

Glucose turnover rates were estimated with [2H2]glucose in five children with glycogen storage disease type I (GSD I) during sequential withdrawal of an infusion of glucose to determine whether their hypoglycemia was the result of decreased glucose production or increased rates of glucose utilization. Plasma glucose concentrations were 78 +/- 5 mg/dl during infusion of glucose at 6 mg X kg-1 X min-1 and decreased to 53 +/- 3 and 45 +/- 7 mg/dl during the 3 and 1.5 mg X kg-1 X min-1 glucose infusions, respectively. Total glucose flux during the 6 mg X kg-1 X min-1 glucose infusion was 7.3 +/- 0.7 mg X kg-1 X min-1 and decreased with reduction in the rate of glucose infused. Endogenous glucose production increased with each decrease in the rate of exogenous glucose infused. Following discontinuation of glucose infusion, endogenous glucose production was 3.9 +/- 0.3 mg X kg-1 X min-1, a value that was lower (P less than 0.05) than that observed in overnight-fasted normal children (6.3 +/- 0.3 mg X kg-1 X min-1) but not statistically different from the Ra of normal children fasted for 30 h (4.1 +/- 0.5 mg X kg-1 X min-1). Thus, children with GSD have glucose production rates that are 40% lower than those of normal children fasted overnight but equal to those of normal children fasted 30 h. Rates of glucose utilization during the 6 mg X kg-1 X min-1 glucose infusion were higher (0.05 less than P less than 0.1) than those of overnight-fasted normal children, despite lower plasma glucose concentrations when expressed on a body weight basis but not when expressed on the basis of estimated brain weight.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1984

Abnormal coupling of insulin receptor binding in noninsulin-dependent diabetes.

By use of the glucose clamp sequential insulin infusion technique, we compared the dose-response characteristics of insulin-mediated glucose disposal in 17 patients with noninsulin-dependent diabetes mellitus (NIDDM) and 13 age- and weight-matched nondiabetic volunteers. In terms of plasma insulin concentrations, the dose-response curve in the diabetics was shifted to the right (Km 156 +/- 28 vs. 58 +/- 4 microU/ml in nondiabetics, P less than 0.01) with a decreased maximum response (Vmax 320 +/- 22 vs. 405 +/- 10 mg X m-2 X min-1 in nondiabetics, P less than 0.01). Moreover, coupling between insulin receptor binding and activation of insulin effector units was defective in the diabetic subjects (half-maximally effective insulin receptor occupancy 184 +/- 11 vs. 145 +/- 12 pg in nondiabetics for monocytes, P less than 0.02, and 120 +/- 8 vs. 85 +/- 4 pg for erythrocytes in nondiabetics, P less than 0.01). The presence of defective coupling in itself could explain the abnormal insulin dose-response characteristics for glucose disposal in NIDDM and differentiates the insulin resistance of this condition from that of obesity in which coupling is normal.

Blood Glucose↗
PubMed1984

Increased proteolysis. An effect of increases in plasma cortisol within the physiologic range.

Prolonged exposure to glucocorticoids in pharmacologic amounts results in muscle wasting, but whether changes in plasma cortisol within the physiologic range affect amino acid and protein metabolism in man has not been determined. To determine whether a physiologic increase in plasma cortisol increases proteolysis and the de novo synthesis of alanine, seven normal subjects were studied on two occasions during an 8-h infusion of either hydrocortisone sodium succinate (2 micrograms/kg X min) or saline. The rate of appearance (Ra) of leucine and alanine were estimated using [2H3]leucine and [2H3]alanine. In addition, the Ra of leucine nitrogen and the rate of transfer of leucine nitrogen to alanine were estimated using [15N]leucine. Plasma cortisol increased (10 +/- 1 to 42 +/- 4 micrograms/dl) during cortisol infusion and decreased (14 +/- 2 to 10 +/- 2 micrograms/dl) during saline infusion. No change was observed in plasma insulin, C-peptide, or glucagon during either saline or cortisol infusion. Plasma leucine concentration increased more (P less than 0.05) during cortisol infusion (120 +/- 1 to 203 +/- 21 microM) than saline (118 +/- 8 to 154 +/- 4 microM) as a result of a greater (P less than 0.01) increase in its Ra during cortisol infusion (1.47 +/- 0.08 to 1.81 +/- 0.08 mumol/kg X min for cortisol vs. 1.50 +/- 0.08 to 1.57 +/- 0.09 mumol/kg X min). Leucine nitrogen Ra increased (P less than 0.01) from 2.35 +/- 0.12 to 3.46 +/- 0.24 mumol/kg X min, but less so (P less than 0.05) during saline infusion (2.43 +/- 0.17 to 2.84 +/- 0.15 mumol/kg X min, P less than 0.01). Alanine Ra increased (P less than 0.05) during cortisol infusion but remained constant during saline infusion. During cortisol, but not during saline infusion, the rate and percentage of leucine nitrogen going to alanine increased (P less than 0.05). Thus, an increase in plasma cortisol within the physiologic range increases proteolysis and the de novo synthesis of alanine, a potential gluconeogenic substrate. Therefore, physiologic changes in plasma cortisol play a role in the regulation of whole body protein and amino acid metabolism in man.

Adult↗
PubMed1984

Defective glucose counterregulation after subcutaneous insulin in noninsulin-dependent diabetes mellitus. Paradoxical suppression of glucose utilization and lack of compensatory increase in glucose production, roles of insulin resistance, abnormal neuroendocrine responses, and islet paracrine interactions.

To characterize glucose counterregulatory mechanisms in patients with noninsulin-dependent diabetes mellitus (NIDDM) and to test the hypothesis that the increase in glucagon secretion during hypoglycemia occurs primarily via a paracrine islet A-B cell interaction, we examined the effects of a subcutaneously injected therapeutic dose of insulin (0.15 U/kg) on plasma glucose kinetics, rates of glucose production and utilization, and their relationships to changes in the circulating concentrations of neuroendocrine glucoregulatory factors (glucagon, epinephrine, norepinephrine, growth hormone, and cortisol), as well as to changes in endogenous insulin secretion in 13 nonobese NIDDM patients with no clinical evidence of autonomic neuropathy. Compared with 11 age-weight matched nondiabetic volunteers in whom euglycemia was restored primarily by a compensatory increase in glucose production, in the diabetics there was no compensatory increase in glucose production (basal 2.08 +/- 0.04----1.79 +/- 0.07 mg/kg per min at 21/2 h in diabetics vs. basal 2.06 +/- 0.04----2.32 +/- 0.11 mg/kg per min at 21/2 h in nondiabetics, P less than 0.01) despite the fact that plasma insulin concentrations were similar in both groups (peak values 22 +/- 2 vs. 23 +/- 2 microU/ml in diabetics and nondiabetics, respectively). This abnormality in glucose production was nearly completely compensated for by a paradoxical decrease in glucose utilization after injection of insulin (basal 2.11 +/- 0.03----1.86 +/- 0.06 mg/kg per min at 21/2 h in diabetics vs. basal 2.08 +/- 0.04----2.39 +/- 0.11 mg/kg per min at 21/2 h nondiabetics, P less than 0.01), which could not be accounted for by differences in plasma glucose concentrations; the net result was a modest prolongation of hypoglycemia. Plasma glucagon (area under the curve [AUC] above base line, 12 +/- 3 vs. 23 +/- 3 mg/ml X 12 h in nondiabetics, P less than 0.05), cortisol (AUC 2.2 +/- 0.5 vs. 4.0 +/- 0.7 mg/dl X 12 h in nondiabetics, P less than 0.05), and growth hormone (AUC 1.6 +/- 0.4 vs. 2.9 +/- 0.4 micrograms/ml X 12 h in nondiabetics, P less than 0.05) responses in the diabetics were decreased 50% while their plasma norepinephrine responses (AUC 49 +/- 12 vs. 21 +/- 5 ng/ml X 12 h in nondiabetics, P less than 0.05) were increased twofold (P less than 0.05) and their plasma epinephrine responses were similar to those of the nondiabetics (AUC 106 +/- 17 vs. 112 +/- 10 ng/ml X 12 h in nondiabetics). In both groups of subjects, increases in plasma glucagon were inversely correlated with plasma glucose concentrations (r = -0.80 in both groups, P less than 0.01) and suppression of endogenous insulin secretion (r = -0.57 in nondiabe

Adult↗
PubMed1984

Abnormal meal carbohydrate disposition in insulin-dependent diabetes. Relative contributions of endogenous glucose production and initial splanchnic uptake and effect of intensive insulin therapy.

Postprandial hyperglycemia in insulin-deficient, insulin-dependent diabetic subjects may result from impaired suppression of endogenous glucose production and/or abnormal disposition of meal-derived glucose. To investigate the relative contributions of these processes and to determine whether 2 wk of near normoglycemia achieved by using intensive insulin therapy could restore the pattern of glucose disposal to normal, meal-related and endogenous rates of glucose appearance were measured isotopically after ingestion of a mixed meal that contained deuterated glucose in seven lean insulin-dependent and five lean nondiabetic subjects. Diabetic subjects were studied once when insulin deficient and again during intensive insulin therapy after 2 wk of near normoglycemia. Total glucose production was determined by using tritiated glucose and the contribution of meal-related glucose was determined by using the plasma enrichment of deuterated glucose. The elevated basal and peak postprandial plasma glucose concentrations (252 +/- 33 and 452 +/- 31 mg/dl) of diabetic subjects when insulin deficient were decreased by intensive insulin therapy to values (82 +/- 6 and 193 +/- 10 mg/dl, P less than 0.01) that approximated those of nondiabetic subjects (93 +/- 3 and 140 +/- 15 mg/dl, respectively). Total and endogenous rates of glucose appearance (3,091 +/- 523 and 1,814 +/- 474 mg/kg per 8 h) in the diabetic subjects were significantly (P less than 0.02) greater than those in non-diabetic subjects (1,718 +/- 34 and 620 +/- 98 mg/kg per 8 h, respectively), whereas meal-derived rates of glucose appearance did not differ. Intensive insulin therapy decreased (P less than 0.01) both total (1,581 +/- 98 mg/kg per 8 h) and endogenous (478 +/- 67 mg/kg per 8 h) glucose appearance to rates that approximated those observed in the nondiabetic subjects, but did not alter meal-related glucose appearance. Thus, excessive entry of glucose into the peripheral circulation in insulin-deficient diabetic patients after ingestion of a mixed meal resulted from a lack of appropriate suppression of endogenous glucose production rather than impairment of initial splanchnic glucose uptake. Intensive insulin therapy restored postprandial suppression of endogenous glucose production to rates observed in nondiabetic subjects.

Adult↗
PubMed1984

Gastric inhibitory polypeptide in obesity and diabetes mellitus.

Gastric inhibitory polypeptide (GIP) concentrations may be influenced by obesity, diabetes, and glucagon deficiency and be under feedback inhibition by insulin. To assess these factors, insulin-dependent diabetic, totally pancreatectomized diabetic, and lean and obese noninsulin-dependent diabetic patients were studied twice, once during partial insulin withdrawal and again when euglycemia was achieved before and after mixed meal ingestion, using an artificial endocrine pancreas. The results were compared to those from weight-matched lean and obese nondiabetic subjects. No significant differences in postprandial GIP responses were found between lean and obese nondiabetic subjects. Despite basal and postprandial hyperglycemia, the GIP responses to the mixed meal were not significantly different between insulin-deficient (insulin-dependent and totally pancreatectomized) patients and lean nondiabetic subjects. In addition, there were no significant differences in postprandial GIP responses between insulin-dependent and totally pancreatectomized patients. In contrast, lean and obese noninsulin-dependent diabetic patients had reduced GIP responses compared to weight-matched nondiabetic subjects (mean +/- SE, 37.9 +/- 5.4 vs. 67.1 +/- 10.8 ng ml-1 240 min-1, respectively; P less than 0.05). This difference was entirely due to the reduced GIP responses in obese noninsulin-dependent diabetic patients compared to those in obese nondiabetic subjects (32.1 +/- 7.9 vs. 76.9 +/- 18.2 ng ml-1 240 min-1, respectively; P less than 0.05); the postprandial GIP responses were not significantly different between lean noninsulin-dependent diabetic patients and lean nondiabetic subjects. Insulin infusion by an artificial endocrine pancreas resulted in postprandial insulin and glucose profiles that approximated those of nondiabetics, but did not significantly alter GIP responses to the mixed meal (48.2 +/- 5.5 ng ml-1 240 min-1) in the 18 diabetic patients compared to results obtained with sc insulin treatment (42.2 +/- 5.2 ng ml-1 240 min-1). In conclusion, postprandial GIP responses are normal in obese nondiabetic subjects and insulin-deficient diabetic patients and are blunted in obese, but not in lean, noninsulin-dependent diabetic patients. In addition, GIP does not appear to be under feedback inhibition by insulin or influenced by glucagon deficiency in diabetes.

Adult↗
PubMed1984

Demonstration of a dawn phenomenon in normal human volunteers.

To ascertain whether the dawn phenomenon occurs in nondiabetic individuals and, if so, whether it is due to an increase in glucose production or a decrease in glucose utilization, we determined plasma concentrations of glucose, insulin, C-peptide, and counterregulatory hormones, as well as rates of glucose production, glucose utilization, and insulin secretion at one-half-hourly intervals between 1:00 and 9:00 a.m. in eight normal volunteers. After 5:30 a.m., plasma glucose, insulin, and C-peptide concentrations all increased significantly; rates of glucose production, glucose utilization, and insulin secretion also increased (all P less than 0.05). Plasma cortisol, epinephrine, and norepinephrine increased significantly from nocturnal nadirs between 4:00 and 6:30 a.m. Plasma growth hormone, which had increased episodically between 1:00 and 4:30 a.m., decreased thereafter nearly 50% (P less than 0.05). Plasma glucagon did not change significantly throughout the period of observation. These results indicate that a dawn-like phenomenon, initiated by an increase in glucose production, occurs in nondiabetic individuals. Thus, early morning increases in plasma glucose concentrations and insulin requirements observed in IDDM and NIDDM may be an exaggeration of a physiologic circadian variation in hepatic insulin sensitivity induced by antecedent changes in catecholamine and/or growth hormone secretion.

Adult↗
PubMed1984

Effects of long-term optimization and short-term deterioration of glycemic control on glucose counterregulation in type I diabetes mellitus.

To assess the effects of glycemic control on glucose counterregulation, rates of plasma glucose recovery from hypoglycemia and counterregulatory hormonal responses were studied in 18 C-peptide-negative patients with insulin-dependent diabetes mellitus (IDDM) before and after either improvement, no change, or deterioration in glycemic control. Hypoglycemia was induced by an i.v. insulin infusion (30 mU/m2 X min for 1 h) after maintenance of euglycemia overnight with i.v. insulin. In 13 patients with long duration of IDDM (9 +/- 0.5 yr, mean +/- SEM) and initially poor glycemic control (mean diurnal blood glucose, MBG 199 +/- 8 mg/dl, ketoamine-HbA1 12.4 +/- 0.2%; nondiabetic subjects 104 +/- 4 mg/dl and 6.8 +/- 0.09%, respectively), rates of plasma glucose recovery from hypoglycemia (0.30 +/- 0.01 versus 0.60 +/- 0.01 mg/dl X min in nondiabetic subjects, P less than 0.001) and plasma glucagon (AUC 0.56 +/- 0.09 versus 6.3 +/- 0.50 ng/ml X 150 min in nondiabetic subjects, P less than 0.01) and epinephrine (AUC 16.9 +/- 0.2 versus 25.7 +/- 0.2 ng/ml X 150 min in nondiabetic subjects, P less than 0.001) responses to hypoglycemia were impaired. Intensive therapy (three daily injections of insulin) instituted in 7 out of 13 IDDM patients for up to 9 mo improved MBG (124 +/- 6 mg/dl, P less than 0.01) and ketoamine-HbA1 (7.9 +/- 0.02%, P less than 0.01) but not rates of plasma glucose recovery (0.31 +/- 0.01 mg/dl X min) and plasma glucagon (AUC 0.69 +/- 0.07 ng/ml X 150 min) and epinephrine (AUC 14.9 +/- 0.17 ng/ml X 150 min) responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

A reliable and reproducible test for adequate glucose counterregulation in type I diabetes mellitus.

The safety, reproducibility, and reliability of an insulin infusion test for assessment of adequate glucose counterregulation were evaluated in 18 patients with type I (insulin-dependent) diabetes mellitus. When the test (a 60-min, 30-mU/m2/min insulin infusion) was administered on three separate occasions at 3-4-wk intervals, coefficients of variation for plasma glucose and counterregulatory hormone (glucagon, epinephrine, cortisol, and growth hormone) responses averaged less than 8%. No patient experienced symptoms requiring discontinuation of the test and plasma glucose concentrations increased spontaneously after stopping the insulin infusion. Using objective criteria based on plasma glucose nadirs or postnadir rates of plasma glucose recovery, no patient judged to have adequate glucose counterregulation by the test (postnadir rates of plasma glucose recovery or plasma glucose nadir above 0.4 mg/dl/min and 45 mg/dl) developed severe hypoglycemia (plasma glucose less than 40 mg/dl) during up to 7 mo of intensive insulin therapy, whereas nearly all patients with inadequate counterregulation did. We conclude that this test, when performed in standardized conditions, is safe and reproducible and can reliably predict those patients with type I diabetes who are at risk of developing severe hypoglycemia during intensive insulin therapy.

Adolescent↗
PubMed1983

Glucose and ketone body kinetics in diabetic ketoacidosis.

The hyperglycaemia and hyperketonaemia of diabetic ketoacidosis are initiated primarily by overproduction of these substrates; subsequent maintenance of hyperglycaemia occurs, in large part, due to impaired utilization of glucose, whereas overproduction of ketone bodies continues to be the major mechanism for maintenance of hyperketonaemia. Insulin deficiency results in increased rates of lipolysis and provides increased substrate (free fatty acids) for ketogenesis. Hyperglucagonaemia can augment ketogenesis further in the setting of insulin deficiency. It is likely that other counter-insulin hormones (growth hormone, catecholamines) also contribute to the pathogenesis of DKA, though their role is less well defined. Insulin corrects DKA largely via suppression of lipolysis (and thus ketone body production); insulin suppresses glucose production at lower levels than it does ketone body production.

Diabetic Ketoacidosis↗
PubMed1983

Effects of free fatty acid availability, glucagon excess, and insulin deficiency on ketone body production in postabsorptive man.

The present studies were undertaken to assess the relative effects of free fatty acid (FFA) availability, glucagon excess, and insulin deficiency on ketone body (KB) production in man. To determine whether an increase in FFA availability would augment KB production in the absence of insulin deficiency and glucagon excess, plasma insulin and glucagon were maintained at basal concentrations by infusion of somatostatin and exogenous insulin and glucagon, and plasma FFA were increased from 0.32 +/- 0.06 to 1.4 +/- 0.1 mM by a 2.5-h-infusion of a triglyceride emulsion plus heparin. KB production increased fivefold from 2.2 +/- 0.4 to 11.4 +/- 1.2 mumol . kg-1 . min-1, P less than 0.001. To determine whether insulin deficiency would further augment KB production, analogous experiments were performed but the replacement infusion of insulin was stopped. Despite a greater increase in plasma FFA (from 0.26 +/- 0.04 to 1.95 +/- 0.3 mM), KB production increased (from 1.5 +/- 0.3 to 11.1 +/- 1.8 mumol . kg-1 . min-1) to the same extent as in the absence of insulin deficiency. To determine whether hyperglucagonemia would augment KB production beyond that accompanying an increase in plasma FFA and, if so, whether this required insulin deficiency, similar experiments were performed in which the glucagon infusion rate was increased to produce plasma glucagon concentrations of 450-550 pg/ml with and without maintenance of the basal insulin infusion. When basal plasma insulin concentrations were maintained, hyperglucagonemia did not further increase KB production; however, when the basal insulin infusion was discontinued, hyperglucagonemia increased KB production significantly, whereas no change was observed in saline control experiments. These studies indicate that, in man, FFA availability is a major determinant of rates of KB production; insulin does not appear to influence ketogenesis rates by a direct hepatic effect, and glucagon can further augment KB production when FFA concentrations are increased but only in the setting of insulin deficiency.

3-Hydroxybutyric Acid↗
PubMed1983

Prandial insulin requirements in insulin-dependent diabetics: effects of size, time of day, and sequence of meals.

To assess the effects of size, time of day, and sequence of meals on insulin requirements determined by an artificial endocrine pancreas, eight insulin-dependent diabetics ate meals of 12.5%, 25%, and 50% of total calories (30 Kcal/kg) at 0800, 1300, and 1800 on each of 3 separate days in a randomized order in one of two sequences in a three by three Latin square design. Plasma glucose and free insulin concentrations and amounts of insulin infused by the artificial endocrine pancreas were associated with meal size (P less than 0.001) but not with time of day of meal ingestion (analysis of variance). The sequence of meal ingestion did not alter integrated plasma glucose responses, but did influence the meal-related amounts of insulin infused. Thus, consideration should be given to meal size and sequence of meal ingestion but not time of day of meal ingestion when determining prandial iv insulin requirements.

Adult↗
PubMed1983

Abnormal glucose counterregulation in insulin-dependent diabetes mellitus. Interaction of anti-insulin antibodies and impaired glucagon and epinephrine secretion.

To evaluate the roles of counterregulatory hormones and insulin antibodies in the impairment of plasma glucose recovery from hypoglycemia in diabetes mellitus, and to assess the relationship between the glucagon response and duration of the disease, 21 insulin-dependent diabetic patients and 10 nondiabetic subjects were studied. The diabetics consisted of 5 patients with recent onset of diabetes (less than 1 mo); 11 with 2.6 +/- 0.3 (mean +/- SEM) yr duration of diabetes, 5 of whom had insulin antibodies; and 5 patients with long-term diabetes (21 +/- 3 yr), insulin antibodies, and autonomic neuropathy. During insulin-induced hypoglycemia (28 mU/m2 X min for 60 min) in patients with recent-onset diabetes, plasma free insulin, glucose, and counterregulatory hormone concentrations did not differ from those of nondiabetic subjects. In patients with insulin antibodies, the disappearance of insulin after insulin infusion was delayed, and both restitution of normoglycemia and plasma glucagon response were blunted compared with patients without antibodies. When glucagon was infused (80-130 ng/m2 X min) during hypoglycemia in diabetics with impaired glucagon responses in order to simulate normal glucagon responses, plasma glucose recovery was normalized in patients without antibodies but not in those with antibodies. In patients with long-standing diabetes, restitution of normoglycemia was further impaired and this was associated with an absent plasma glucagon response and a diminished plasma epinephrine response. Plasma glucagon responses to hypoglycemia were inversely correlated to the duration of diabetes (r = -0.943; P less than 0.0005). It is concluded that impaired A-cell secretion is the predominant mechanism for the delayed glucose recovery after hypoglycemia in diabetic patients without insulin antibodies and normal epinephrine responses. Slowed disappearance of insulin due to the presence of insulin antibodies further delays the restoration of normoglycemia. Patients with long-standing diabetes and autonomic neuropathy exhibit decreased epinephrine secretion, which leads to an additional retardation of glucose recovery. Since plasma glucagon and epinephrine responses to hypoglycemia were normal at the onset of diabetes but diminished in long-term diabetes, it appears that the impaired glucagon and epinephrine responses to hypoglycemia are acquired defects that develop subsequent to B-cell failure.

Adolescent↗
PubMed1983

Failure of infused beta-hydroxybutyrate to decrease proteolysis in man.

Ketone bodies have been suggested to have a protein-sparing effect, since infusion of Na-beta-hydroxybutyrate in man decreases plasma alanine concentrations and urinary nitrogen (N) excretion. To test this hypothesis, six normal postabsorptive volunteers were infused with Na-beta-hydroxybutyrate for 3 h. Rates of glucose, leucine carbon, and alanine appearance and disappearance from the plasma space were traced with [3-3H]glucose, L-[6,6,6-2H3]leucine, and [2,3,3,3-2H4]alanine. Rates of leucine N appearance and disappearance and the rate of transfer of leucine N to alanine were assessed with [15N]leucine. During ketone body infusion, plasma alanine decreased (P less than 0.05), whereas plasma leucine increased (P less than 0.05). Rates of alanine appearance increased (5.3 +/- 0.3 to 7.8 +/- 0.6 mumol/kg X min), but the increase in its rate of disappearance was slightly greater, accounting for the decrease in plasma alanine concentration. Leucine N flux and the rate and percent of leucine N transferred to alanine increased, whereas leucine carbon flux was unchanged. To determine the effect of the alkalemia induced by Na-beta-hydroxybutyrate, four additional subjects were infused with NaHCO3. Alkalemia had no effect on leucine N or carbon flux or on the rate of appearance of alanine, but increased the rate of alanine disappearance, resulting in a decrease in the plasma alanine concentration. Since the rate of appearance of leucine carbon was unaltered during the infusion of Na-beta-hydroxybutyrate, it is unlikely that hyperketonemia per se decreases proteolysis in postabsorptive man.

3-Hydroxybutyric Acid↗