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Biomedical subjects

M A Sperling

Publications and source records attributed to M A Sperling.

At least 55 records · Page 3Linked to original sources
PubMed1988

Circulating catecholamines and glucagon in infants of strictly controlled diabetic mothers.

Previous studies have demonstrated impaired perinatal adaptation of glucose homeostasis with inappropriately low levels of catecholamines and glucagon in newborn infants born to diabetic mothers. To investigate whether these neonatal changes are related to maternal metabolic control, we sequentially measured plasma glucose, catecholamines and glucagon in the neonatal period in 10 infants born to well-controlled mothers with class B diabetes mellitus after uncomplicated pregnancies. Good glycemic control in the mothers resulted in appropriate counterregulatory hormone responses in the neonatal period, similar to those described in infants born to normal mothers. The significant rise in plasma epinephrine and glucagon paralleled the establishment of euglycemia, further suggesting that these hormones are important for perinatal adaptation of glucose homeostasis.

Blood Glucose↗
PubMed1988

Carbohydrate metabolism.

In summary, the surges of glucagon and epinephrine at birth, coupled with the fall in insulin secretion, are in accord with appropriate receptor changes, as well as genetic ontogenic patterns of enzyme development. Enzyme activities are further stimulated by the hormonal changes at birth; phosphorylase is activated by glucagon and epinephrine, while PEPCK is activated by glucagon and its expression is facilitated by the fall in insulin. In concert, these changes permit rapid activation of catabolic processes and the mobilization and utilization of endogenous fuel stores. Glucose homeostasis is maintained by glycogenolysis and gluconeogenesis supported by the appropriate enzyme inductions. The free fatty acids released, via lipolysis, also serve to sustain gluconeogenesis, since hepatic fatty acid oxidation is necessary for gluconeogenesis by providing the essential cofactors. This framework permits a rational interpretation of the mechanisms underlying the remarkable transition from intrauterine dependence on maternal glucose to extrauterine autonomy of newborn energy integration. This framework can also explain several causes of neonatal hypoglycemia and act as a base for future investigations.

Animals↗
PubMed1987

The regulation of basal pancreatic polypeptide levels in dogs.

In response to various stimuli, pancreatic polypeptide (PP) release is predominantly mediated by cholinergic mechanisms, and may be modulated by sympathetic and opiate (inhibitory) effects. However, the mechanisms regulating basal PP levels remain unclear. We examined the possible role of the sympathetic nervous system and endogenous opiates in the regulation of basal levels of pancreatic polypeptide in trained conscious dogs. During prolonged (150 min) alpha- or beta-adrenergic blockade with phentolamine and propranolol, separately or in combination, there was no change in the basal PP levels of 154 +/- 20 pg/ml. Effective adrenergic modulation of pancreatic hormones was evident since alpha blockade led to a rise in insulin and glucagon, beta blockade led to a fall in insulin and glucagon, while combined alpha- and beta-adrenergic blockade did not affect insulin or glucagon. Opiate blockade with naloxone (1.25 mg followed by 1 microgram/kg/min) led to a delayed fall in PP from 153 +/- 22 to 89 +/- 15 pg/ml at 90 min (no change by 30 min), without a change of insulin or glucagon. Infusion of a potent morphine analogue D-Met2-Pro5-enkephalinamide (0.5 microgram/kg/min) led to a sustained fall in PP to 91 +/- 8 pg/ml by 30 min without a change in insulin or glucagon. Somatostatin infusion (0.2 microgram/kg/min) with insulin and glucagon replacement, led to a similar sustained fall in PP. It is concluded that in dogs: in contrast to insulin and glucagon, at basal conditions the plasma level of PP is not modulated by endogenous alpha- or beta-adrenergic influences.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Puberty decreases insulin sensitivity.

Puberty is commonly associated with an increase in insulin requirement in patients with insulin-dependent diabetes. To investigate whether this pubertal increase in insulin requirement is confined to diabetic subjects, we examined insulin responses during oral glucose tolerance testing with glucose loads per unit weight (1.75 g/kg) or unit surface area (55 g/m2), and insulin sensitivity via euglycemic-hyperinsulinemic clamp in prepubertal and pubertal children without diabetes. Irrespective of glucose dose, glucose tolerance testing elicited a threefold greater insulin response, but equivalent euglycemia, in pubertal versus prepubertal children (P less than 0.05). As assessed by the clamp procedure, prepubertal children were approximately 30% more sensitive than their pubertal counterparts (P less than 0.01). Insulin sensitivity correlated inversely with body mass index (r = -0.49, P less than 0.02), serum dehydroepiandrosterone sulphate concentration (r = -0.57, P less than 0.01), and log somatomedin C/insulinlike growth factor I (r = -0.45, P less than 0.05). We conclude that puberty is associated with decreased sensitivity to insulin that normally is compensated for by increased insulin secretion. Thus, in patients with insulin-dependent diabetes, an approximately 30% increase in insulin dosage should be anticipated with the onset of puberty.

Adolescent↗
PubMed1987

Pathogenesis of early neonatal hypocalcemia: studies of serum calcitonin, gastrin, and plasma glucagon.

In 64 maternal-infant pairs, we tested the hypotheses that serum calcitonin, serum gastrin, and plasma glucagon concentrations are elevated in infants at risk for early neonatal hypocalcemia, and that elevated serum gastrin and plasma glucagon result in elevated serum calcitonin and low serum calcium values in neonates. Serum Ca declined significantly in neonates at 24 hours of age, and was inversely correlated with serum calcitonin. Cord serum calcitonin, gastrin, and plasma glucagon concentrations rose significantly at 24 hours of age. Cord calcitonin was significantly higher in preterm compared with term infants, and there was no significant difference between asphyxiated and nonasphyxiated preterm neonates; in term neonates cord calcitonin concentration was inversely correlated with Apgar scores at 1 and 5 minutes. Cord calcitonin was not correlated with cord gastrin or glucagon. Cord and 24-hour gastrin and glucagon values were not related to prematurity; cord glucagon, but not gastrin, was related to birth asphyxia. We conclude that (1) serum calcitonin, gastrin, and plasma glucagon values rise postnatally; cord calcitonin is elevated in preterm and in asphyxiated term infants; serum calcitonin concentration does not correlate with the elevated serum gastrin and plasma glucagon values; and at 24 hours of age, decreased serum Ca is correlated with serum calcitonin, and hence calcitonin might play a role in the pathogenesis of early neonatal hypocalcemia.

Apgar Score↗
PubMed1987

Outpatient management of diabetes mellitus.

Outpatient encounters form the mainstay of managing type I diabetes mellitus in children and adolescents. Management philosophy rests on the premise that normal physical and emotional growth is attainable and long-term complications minimized by maintenance of metabolic (glycemic) control. Management principles involve a coordinated team approach of physician, nurse-educator, and dietitian interacting with the family unit to educate them in the appropriate use and adjustment of insulin regimens, to recognize and treat the Somogyi and dawn phenomena, adjustment of nutritional needs, short- and long-term monitoring via home blood glucose and glycosylated hemoglobin measurements, and clues from the history and physical examination that permit anticipatory or reactive steps to achieve the treatment goals.

Adolescent↗
PubMed1987

Characteristics of hepatic receptors for somatomedin-C/insulin-like growth factor I and insulin in the developing human.

Insulin and the somatomedins (Sms) are putative regulators of cell proliferation and metabolism in the fetus. Since the liver is a potential target tissue of these hormones during fetal life, we characterized the hepatic receptors for Sm-C/insulin like growth factor I (Sm-C/IGF-I) and insulin during the second trimester of human fetal development. Membrane-enriched fetal liver homogenates specifically bound 8.9 +/- 1.5% (+/- SD) of added [125I]insulin and 5.1-7.2% of [125I]Sm-C/IGF-I. Binding of both hormones was constant from 12-20 weeks gestation and was much greater than that in adult liver membranes. Analysis of dose-response data indicated high affinity between each receptor and its respective ligand (Kd for the Sm-C/IGF-I receptor, 2.2 X 10(-10) M; Kd for insulin receptor, 5.2 X 10(-10) and 7.7 X 10(-9) M). Limited cross-reactivity (approximately 1:1,000) of insulin with the Sm-C/IGF-I receptor and Sm-C/IGF-I with the insulin receptor was found. Affinity labeling studies showed that each receptor possessed an approximately 135,000-dalton subunit which was a part of a larger disulfide-linked complex. Thus, the human fetal liver has specific receptors for Sm-C/IGF-I and insulin that are similar to those described for other tissues in terms of both hormone-binding characteristics and subunit structure, suggesting that these receptors mediate important cellular functions at this stage of fetal development.

Affinity Labels↗
PubMed1986

Effects of fetal insulin infusion on glucose kinetics in pregnant sheep: a compartmental analysis.

A three-compartment model, consisting of fetus (F), uteroplacenta, and mother (M) was applied to quantitate the effects of fetal hyperinsulinemia on glucose kinetics in pregnant sheep late in gestation. The approach combines the Fick principle with isotope dilution of differentially labeled glucose isotopes, infused simultaneously to F [U-14C]- and M [2-3H]glucose. In the basal state, rates of umbilical glucose uptake (8.37 +/- 0.98 mg/kg per min) and fetal glucose utilization (7.38 +/- 1.13) were equivalent (mean +/- SE; n = 12). When fetal insulin was increased from 13.7 +/- 2.2 to a plateau of approximately 100 microU/ml, arterial glucose decreased from 18.9 +/- 0.8 to a new steady state of approximately 13 mg/dl (P less than 0.001). Whereas umbilical glucose uptake increased at 90 min and remained elevated thereafter (P less than 0.01), fetal glucose utilization increased only transiently at 60 min by 1.9 +/- 0.8 mg/kg per min (26%; P less than 0.05) and then returned to base line. Insulin's persistent effect, however, was evident from the sustained doubling of the glucose clearance rate from 39.3 +/- 5.9 to 66.6 +/- 10.5 ml/kg per min (P less than 0.005). No endogenous fetal glucose production was evident throughout the experiments. Maternal glucose production and utilization remained unchanged, although there was a small decline in M glucose concentration and an increase in glucose transfer from M to the uteroplacenta and F, from 33.9 +/- 8.1 to 48.1 +/- 7.0 mg/min at 60 min (P less than 0.01 by paired analysis). We conclude that fetal hyperinsulinemia initially lowers glucose concentration by transiently increasing fetal glucose utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Insulin stimulates amino acid and lipid metabolism in isolated fetal rat hepatocytes.

Although fetal hyperinsulinemia is associated with excessive deposition of glycogen in liver, both in vivo and in vitro studies show little effect of insulin on glycogen synthesis from glucose or the activity of the enzyme glycogen synthase in the fetus. To investigate whether lack of insulin effect extends to other fetal metabolic processes, we compared the influence of insulin on amino acid uptake (14C-alpha-aminoisobutyric acid) and lipid synthesis [14C-acetate) in freshly isolated hepatocytes from 21-day fetal (F) and adult (A) rats. Viability of F and A hepatocytes was documented by trypan blue exclusion (greater than 90%). In A, insulin stimulated 14C-alpha-aminoisobutyric acid uptake in a dose dependent manner with an apparent Km at 2 ng/ml and a Vmax at 10 ng/ml. When corrected for cell surface area, F cells responded to insulin in a similar dose response manner, although absolute values per 1 X 10(6) cells always remained lower. In contrast, whereas A cells demonstrated a typical dose dependent response of 14C-acetate incorporation into lipid with a Km at 5 ng/ml and Vmax at 10 ng/ml of insulin, F cells remained totally unresponsive when the concentration of acetate was 5 mM or less. However, at higher medium acetate concentrations (15-30 mM) fetal responses were equal to or greater than that of adult, both basally and with insulin. These findings suggest differences in the maturation of insulin-mediated processes in fetal rat hepatocytes; effects on amino acid uptake appear earlier than those on lipid or glycogen synthesis.

Amino Acids↗
PubMed1985

Opiate modulation of glucose turnover in dogs.

We examined the effect of opiate infusion and of opiate blockage on glucose turnover in the basal state, using isotope dilution techniques in trained conscious dogs (n = 5). After a primed-continuous infusion of 3-3H glucose to steady state specific activity (90 minutes), infusion of one of the following was given: D-met2 pro5 enkephalinamide (DMPE), a potent morphine-like opiate, 0.5 mus g/kg/min; naloxone, an opiate antagonist, 1.25 mg followed by 10 mus g/min; or saline control. Infusion of DMPE led to a fall in glucose from 92 +/- 3 to 87 +/- 3 mg/dL by 60 minutes (P less than 0.05), associated with a rise in glucose utilization (Rd) from 3.0 +/- 0.4 to 3.9 +/- 0.6 mg/kg/min by 30 minutes (P less than 0.05); a transient rise in glucose production (Ra; from 3.2 +/- 0.4 to 4.3 +/- 0.4 mg/kg/min; P less than 0.05). Changes in counterregulatory hormones did not account for these findings; insulin was unchanged during all infusions; glucagon showed small late rises at 75 minutes during both DMPE and naloxone infusion; cortisol rose by 30 and 15 minutes, respectively, of DMPE and naloxone infusion; epinephrine rose transiently after 5 minutes of naloxone but was unchanged during DMPE, and norepinephrine was unchanged throughout. Saline infusion had no effects on any of these indices. We conclude that a potent opiate with morphine-like effects (DMPE) can lower glucose in dogs by enhancing peripheral glucose utilization independently of hormonal changes.

Animals↗
PubMed1985

Indomethacin and salicylate decrease epinephrine-induced glycogenolysis.

Epinephrine (E) produces an immediate (0-30 minutes) rise in hepatic glucose production (Ra), largely due to activation of glycogenolysis; thereafter, E-stimulated gluconeogenesis becomes the major factor maintaining glucose production. To investigate the possible role of arachidonic acid metabolites on Ra during E stimulation, we infused E in trained conscious dogs before and during administration of two inhibitors of arachidonic acid metabolism, indomethacin (INDO) and salicylate (S). On separate days, experimental animals were treated with both oral and IV INDO and oral acetylsalicylic acid and IV sodium salicylate. Ra and glucose utilization (Rd), both in mg x kg-1 min-1, were calculated by isotope dilution using 3-3H-glucose. After achieving steady state specific activity, control (C) and experimental animals (n = 6 per group) received E (0.1 ug x kg-1 min-1) for 150 minutes, raising plasma levels to approximately 1500 pg/mL in each group. In C, plasma glucose (G; mg/dL) rose by 17 +/- 5 at 10 minutes and 19 +/- 3 at 20 minutes due to an initial spike in Ra (2.7 +/- 0.2 to 4.9 +/- 0.5; P less than 0.01) at 10 minutes. INDO and S treatment attenuated this initial (10-20 minutes) rise in G (P less than 0.05) due to a lower stimulated Ra at 10 minutes (3.3 +/- 0.1 with INDO; 3.0 +/- 0.5 with S; P less than 0.05). After 20 minutes Ra was not different in the 3 groups; no overall differences in Rd, glucose clearance, or plasma insulin levels occurred with INDO or S treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Endocrine disorders in children.

The childhood endocrine disorders in which surgical intervention is a common or indispensable part of management are succinctly reviewed. Pathophysiology and rational approaches to diagnosis are emphasized.

Adrenal Cortex Neoplasms↗
PubMed1985

Indomethacin and salicylate modulate effect of insulin on glucose kinetics in dogs.

We studied insulin's effects on glucose production (Ra) and utilization (Rd) in trained, conscious dogs before and during treatment with indomethacin (Indo) and salicylate (S). Ra and Rd (mg X kg-1 X min-1) were calculated by isotope dilution using [3-3H]glucose. Animals were treated with either oral Indo or acetylsalicylic acid for 1 day before the respective studies. On the study day, experimental animals were given a continuous infusion of either saline (control), Indo (5 mg/kg bolus followed by 0.05 mg X kg-1 X min-1), or sodium salicylate (0.45 mg X kg-1 X min-1) for 330 min on separate days; each animal participated in all three protocols. After establishing steady-state specific activity, control (C) and experimental animals (n = 6/group) received insulin, 0.275 mU X kg-1 X min-1 for 150 min, raising serum insulin levels two- to threefold above basal. During insulin infusion in C, plasma glucose (G) fell from 99 +/- 2 to 82 +/- 6 ml/dl (P less than 0.01), associated with a transient fall in Ra from 2.5 +/- 0.3 to 1.9 +/- 0.2 (P less than 0.01) at 30 min, returning to base line at 45 min; Rd did not change. In the Indo and S groups, G also fell by a similar extent. In contrast to C, however, the fall in G was associated with a rise in Rd, commencing at 30 min in the Indo group (P less than 0.05) and at 45 min in the S group (P less than 0.01); Ra did not fall and actually rose above basal (P less than 0.05), although it did not match the rise in Rd.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Opiates modulate insulin action in vivo in dogs.

To investigate the influence of opiates on insulin action in vivo, we induced mild physiological hyperinsulinaemia (15-20 mU/l) in five trained conscious dogs in the absence or presence of ongoing infusion with the opiate agonist D-met2-pro5-enkephalinamide (DMPE, 0.5 micrograms X kg-1 X min-1), or the opiate antagonist naloxone (1.25 mg followed by 1 microgram X kg-1 X min-1). The effects on glucose production and glucose utilization were measured by isotope dilution using 3-3H-glucose. Glucose fell similarly over 30 min in response to insulin in controls (0.021 +/- 0.003 mmol X l-1 X min-1), and both the DMPE and naloxone studies (0.016 +/- 0.002 mmol X l-1 X min-1 and 0.017 +/- 0.003 mmol X l-1 X min-1, respectively). In control dogs, insulin lowered glucose by transiently suppressing production by 0.028 +/- 0.006 mmol X kg-1 X min-1 at 20-30 min without changing utilization. In contrast, in both the DMPE and naloxone studies insulin lowered glucose by markedly raising utilization at 20 min by 0.094 +/- 0.017 and 0.139 +/- 0.022 mmol X kg-1 X min-1, respectively. Furthermore, insulin failed to suppress production in both DMPE and naloxone studies and, as plasma glucose fell, production rose in both treatment groups at 20 min by 0.045 +/- 0.012 and 0.089 +/- 0.022 mmol X kg-1 X min-1 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Diabetic ketoacidosis.

In the past decade, considerable advances have occurred in our understanding of the pathophysiology of this disorder, its metabolic sequelae, and its management, particularly with respect to continuous low-dose insulin infusion and the potential benefits of phosphate. This article reviews these advances as they pertain to children.

Bicarbonates↗
PubMed1984

Glucagon and glucose dynamics in sheep: evidence for glucagon resistance in the fetus.

We compared the effects of glucagon infused at 5 and 50 ng X kg-1 X min-1 on glucose turnover (GT), production (Ra), and utilization (Rd) in the fetal (F; n = 5, gestation 129 +/- 3 days, term approximately 150 days) and nonpregnant adult (A; n = 5 and 6) sheep. Infusion of glucagon at 5 ng X kg-1 X min-1 raised fetal glucagon levels (IRG) from a basal of 168 +/- 27 to a mean sustained level of 863 +/- 160 pg/ml but had no effect on basal levels of glucose (G) of 12 +/- 3 mg/dl, insulin (IRI) of 16 +/- 3 microU/ml, GT of 21 +/- 1.3 mg/min, and Rd of 15 +/- 2 mg/min; Ra remained negligible. When fetal IRG was raised to a mean sustained level of 1,809 +/- 210 pg/ml by infusion of glucagon at 50 ng X kg-1 X min-1, G doubled to 23 +/- 1.5 mg/dl, IRI rose to 21 +/- 0.9 microU/ml, GT rose to 60 +/- 5 mg/min, Rd to 30 +/- 4.8 mg/min, and Ra to 41 +/- 6 mg/min (P less than 0.01 for each) indicating induction of F glucose production so that GT was now derived from endogenous sources. By contrast, when IRG levels were raised from 109 +/- 10 to 538 +/- 43 pg/ml by infusion of 5 ng X kg-1 X min-1 to A, basal G rose from 56 +/- 2 to 88 +/- 6 mg/dl, IRI from 24 +/- 2 to 45 +/- 6 microU/ml, GT and Ra from 93 +/- 7 to 173 +/- 17 mg/min, and Rd from 93 +/- 7 to 148 +/- 12 mg/min (P less than 0.01 for each). No further increments of these indexes occurred in A when IRG was raised to a mean sustained level of 2,275 +/- 135 pg/ml by infusion of 50 ng X kg-1 X min-1. These results indicate a relative resistance in F to the glycemic effects of glucagon, consistent with previously demonstrated decreases of hepatic glucagon receptors and glucagon-stimulated cAMP production in fetal liver.

Animals↗
PubMed1984

Fetal-perinatal catecholamine secretion: role in perinatal glucose homeostasis.

Secretion of catecholamines may play an important role in several of the adaptations that characterize the transition from intra- to extrauterine life including cardiovascular, respiratory, and metabolic events, specifically the initiation of endogenous glucose production following curtailment of the transplancental maternal supply of glucose. Maturation of neural and enzymatic pathways involved in catecholamine secretion occurs late in gestation; fetal hypoxia can produce a 20- and 125-fold increase in plasma epinephrine (E) and norepinephrine (NE), respectively. Estimates of turnover (approximately 2,000 pg X kg-1 X min-1) and metabolic clearance rates (20-40 ml X kg-1 X min-1) indicate active secretion and metabolism of E from fetal sources with negligible transfer from the mother. Simultaneously, there is maturation of functional alpha- and beta-adrenergic receptors. At birth, plasma E and NE rise three- to tenfold; plasma levels are higher in hypoxic infants and lower in prematures. Concurrently, glucagon increases three- to fivefold; cortisol and growth hormone also are high, whereas insulin remains low and poorly responsive to stimuli; the number of glucagon receptors increases, whereas that of insulin decreases. Acting in concert these hormonal changes activate glycogenolysis, gluconeogenesis, lypolysis, and ketogenesis. Glucose production and gluconeogenesis, absent in utero, become evident within hours of birth in both humans and sheep. The spontaneous surge in catecholamine secretion at birth may be the key event because infusion of E or NE to fetal sheep in late gestation simulates the metabolic and hormonal profile of glucagon and insulin as well as glucose production that normally only occur with separation of the placenta.

Animals↗