Biomedical subjects

J B Halter

Publications and source records attributed to J B Halter.

At least 55 records · Page 3Linked to original sources

PubMed1994

Hyperinsulinemia prevents prolonged hyperglycemia after intense exercise in insulin-dependent diabetic subjects.

Hyperglycemia with accompanying hyperinsulinemia occurs after brief, greater than 85% maximum oxygen consumption exercise to exhaustion in normal subjects and persists up to 60 min of recovery. To determine the importance of endogenous insulin secretion during and after intense exercise, responses to exercise of lean fit male post-absorptive insulin-dependent diabetes mellitus (IDDM) subjects, aged 18-34 yr, were compared with those of control subjects (C; n = 6). Three iv insulin protocols were employed: hyperglycemic (HG; n = 7) and euglycemic (EG1; n = 6) with constant insulin infusion, and euglycemic with doubled insulin infusion during recovery (EG2; n = 6). Overnight iv insulin was adjusted to achieve prolonged euglycemia (5.4 +/- 0.3 mmol/L) or hyperglycemia (8.6 +/- 0.3 mmol/L) before exercise. This allowed for comparisons between HG and EG1 (constant infusion) and between C and EG2 (to approximate physiological hyperinsulinemia by doubling the infusion rates at exhaustion for 56 +/- 7 min during recovery). Subjects exercised to 89-98% of their individual maximum oxygen consumption for 12.8 +/- 0.3 min. Glycemia increased to maximum values at 6 min of recovery (9.8 +/- 0.5 in HG, 6.9 +/- 0.4 in EG1, 7.3 +/- 0.3 in EG2, and 6.9 +/- 0.4 mmol/L in C). Whereas in EG2 and C, glucose returned to resting values in 50-80 min, it remained elevated at 120 min recovery in HG and EG1. During exercise, [3-3H]-glucose-determined glucose production increased markedly and exceeded disappearance in all groups, but less so in the HG subjects than in the other groups. An early recovery decline in glucose production did not differ among groups, but MCR (rate of glucose disappearance/glycemia) were markedly lower in HG and EG1, in whom plasma free insulin remained unchanged from 15 min of recovery onward (MCR, 1.6-1.9 vs. 2.3-2.8 mL/kg.min in C). Doubling the insulin infusion rate in EG2 restored the MCR response to that of C subjects. In summary, constant insulin infusion is insufficient to prevent prolonged postexercise hyperglycemia in IDDM subjects, even when provided at a rate sufficient to maintain normal resting glycemia and glucose turnover. The finding that increasing the rate of insulin infusion restored plasma glucose to normal in IDDM subjects suggests that the postexercise increase in insulin levels observed in normal subjects is essential to return plasma glucose to resting levels. Therefore, special strategies, differing from those for less strenuous exercise, are required for the management of insulin therapy in IDDM during and after intense exercise.

Adolescent↗

PubMed1994

Abnormal insulin secretion, not insulin resistance, is the genetic or primary defect of MODY in the RW pedigree.

Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus (NIDDM) associated with autosomal-dominant inheritance. In the RW pedigree, MODY is associated with polymorphic DNA markers on chromosome 20q. To determine the early abnormalities of insulin action and insulin secretion in MODY, we studied nondiabetic members of the RW pedigree with and without the gene marker. Six nondiabetic marker-negative and 5 nondiabetic marker-positive members of the RW pedigree were studied, as were 4 diabetic marker-positive family members. Unrelated, young, healthy subjects served as comparison groups. Insulin action and insulin secretion were assessed with a frequently sampled intravenous glucose tolerance test. Insulin secretion was further assessed during constant glucose infusion by deconvolution of plasma C-peptide and by pulse analysis. The nondiabetic marker-positive group had normal sensitivity to insulin and unimpaired acute insulin response to intravenous glucose (AIRglu). However, the nondiabetic marker-positive group had decreased mean plasma C-peptide concentration and reduced absolute amplitude of insulin secretory oscillations during prolonged glucose infusion. These responses to prolonged glucose infusion were similar to those observed in the diabetic group. No alterations of insulin secretion were observed in the nondiabetic marker-negative family members. Deranged and deficient insulin secretion, and not insulin resistance, appears to be the genetic or primary abnormality that characterizes nondiabetic individuals who are predisposed to MODY in the RW pedigree.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

The role of liver glucosensors in the integrated sympathetic response induced by deep hypoglycemia in dogs.

The significance of the portohepatic glucosensors for counterregulation in deep hypoglycemia (i.e., glycemia < 2.8 mM) was studied in chronically cannulated male mongrel dogs in the conscious state. A total of 16 experiments were carried out on 6 dogs using the liver clamp technique under hyperinsulinemic conditions (insulin infusion, 39 pmol.min-1.kg-1, 0-150 min). The level of glycemia presented to the liver was made to differ from the systemic arterial glucose level via portal glucose infusion. Tracer-determined rates of glucose clearance and hepatic glucose output (HGO) were assessed using D-[3-3H]glucose (0.26 microCi.min-1). Three protocols were used. In protocol I, liver clamp, systemic hypoglycemia at 2.60 +/- 0.09 mM, and liver glycemia at 3.86 +/- 0.05 mM were achieved with portal glucose infusion (28.2 +/- 3.0 mumol.min-1.kg-1). For protocol II, glucose was infused peripherally (18.2 +/- 4.3 mumol.min-1.kg-1), while systemic and liver glycemia were sustained at deep hypoglycemia, 2.50 +/- 0.08 mM. In protocol III, via peripheral glucose infusion (62.9 +/- 5.8 mumol.min-1.kg-1), systemic and liver glycemia were maintained at a level matched to the liver glycemia during protocol I (3.98 +/- 0.05 mM, P > 0.10). When compared with protocols I and III, the catecholamine response above basal was significantly greater during protocol II with liver and systemic deep hypoglycemia (7.30 +/- 1.51 and 2.89 +/- 0.5 nM for epinephrine and norepinephrine, respectively, P < 0.005). These values reflect net increases in the catecholamine responses of 100% and 85% for epinephrine and norepinephrine when compared with protocol I.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Aging and insulin sensitivity: role of blood pressure and sympathetic nervous system activity.

BACKGROUND: The purpose of this study was to determine whether age is a predictor of sensitivity to the peripheral effects of insulin on carbohydrate metabolism independent of the potential influences of the level of sympathetic nervous system (SNS) activity and blood pressure (BP). METHODS: In 60 human subjects (age range 19-78 years), insulin sensitivity, SI, was determined from glucose and insulin levels obtained during an intravenous glucose tolerance test, and plasma norepinephrine (NE) levels were measured to estimate SNS activity. RESULTS: There were age-associated increases in plasma NE level (r = .585; p < .001) and mean arterial BP (r = .516; p < .001), and an age-associated decline in SI (r = -.352; p = .04). However, in stepwise multiple regression analysis, body mass index (BMI) and mean arterial BP were the only independent predictors of SI, accounting for 43% of the variance in SI; age, plasma NE level, plasma epinephrine level, and fasting plasma glucose did not enter the model. Although these results suggest an age-associated decline in insulin sensitivity, this decline appears to be associated with BMI and mean arterial BP rather than aging per se. In addition, the age-associated increase in SNS activity was not found to be an independent predictor of insulin sensitivity. CONCLUSION: This study demonstrates that in addition to BMI, blood pressure should be considered as another confounding factor in studies of insulin sensitivity in human aging.

Adult↗

PubMed1993

The roles of insulin and catecholamines in the glucoregulatory response during intense exercise and early recovery in insulin-dependent diabetic and control subjects.

Intense exercise is associated with a marked stimulation of glucose production (Ra), a somewhat smaller increment in its utilization (Rd) (and therefore hyperglycemia), large increases in plasma catecholamines, and moderate hyperglucagonemia. The hyperglycemia increases in recovery and is accompanied by hyperinsulinemia. Because these adaptations are unique to intense exercise, we tested the physiological significance of the hyperinsulinemia by exercising six fit, postabsorptive young male subjects with insulin-dependent diabetes mellitus (IDDM) after overnight glycemic normalization by iv insulin, keeping its infusion rate constant during and for 2 h after 100% maximum VO2 cycle ergometer exercise to exhaustion (12 min) (no postexercise hyperinsulinemia). Their responses were compared with those of matched control subjects studied on two separate occasions, once without intervention (physiological hyperinsulinemia, n = 6) and again with a 0.05 U/kg iv bolus at exhaustion (postexercise supraphysiological hyperinsulinemia, n = 5). In all three study protocols, Ra increased by 7-fold, and Rd by 4-fold at exhaustion, and Ra declined in early recovery at the same rates. Therefore, the early recovery hyperinsulinemia is not required to return Ra to preexercise levels, and excessive hyperinsulinemia does not accelerate this decline. We infer that the catecholamine increments and decrements are the prime regulators of Ra (correlations of Ra vs. norepinephrine or epinephrine, P < 0.001 in the three studies), with a smaller contribution from the concurrent hyperglucagonemia. Rd, in contrast, was significantly affected by insulin. In the IDDM subjects, Rd remained at the same rate as Ra through most of recovery, resulting in sustained hyperglycemia and decreased glucose MCR, vs. the control subjects. This hyperglycemia compensated for the abnormal MCR, such that Rd was comparable to that in the control subjects. With the insulin bolus, the Rd elevation was sustained longer compared to the study without bolus, resulting in mild hypoglycemia successfully counterregulated by an increase in Ra. Thus, the principal regulators of the marked exercise increase and rapid recovery decrease in Ra are probably the catecholamines. The postexercise hyperinsulinemia is required for the MCR response and to return plasma glucose concentrations to preexercise levels. Different therapeutic strategies are required in persons with IDDM undergoing strenuous vs. moderate exercise, because of their inability to generate the postexercise hyperinsulinemia.

Adult↗

PubMed1993

Effects of epinephrine on insulin secretion and action in humans. Interaction with aging.

This study was designed to define the effects on glucose metabolism of small increases of plasma EPI, comparable to increases observed during physiological sympathoadrenal activation. This study was also designed to determine the effects of EPI on glucose metabolism in older adults, in whom changes in adrenergic responsiveness of several tissues were described. Tolbutamide-boosted IVGTTs were performed during intravenous infusions of saline (control) or EPI at 2.7, 5.5, and 10.9 mmol/min to achieve physiological levels of EPI in 7 young subjects (19-26 yr of age) and 7 old subjects (62-75 yr of age), all with a normal screening OGTT. IVGTT results were analyzed to determine the AIR and with the minimal model method of Bergman to determine SI and SG. A significant fall was observed in AIR, SI, and SG for all subjects, even with the lowest dose of EPI, which resulted in only a two- to threefold increase in plasma EPI. Older subjects had a delayed recovery from hyperglycemia during the EPI infusions, although we detected no significant differences between the young and old subjects in the ability of EPI to alter either acute phase insulin secretion or insulin action. In contrast, the impairment of SG by EPI appeared to be greater in the elderly. We conclude that small increases of plasma EPI can significantly affect determinants of glucose tolerance in both young and old people.

Adult↗

PubMed1992

Preserved insulin secretion and insulin independence in recipients of islet autografts.

BACKGROUND: Transplantation of pancreatic islets, rather than whole pancreas, has been introduced as a treatment for diabetes mellitus. We studied five patients ranging in age from 12 to 37 years who had severe chronic pancreatitis for which they underwent total pancreatectomy followed by isolation and hepatic transplantation of their own islets. METHODS: All patients had remained insulin-independent for 1 to 7 1/2 years after transplantation. The numbers of islets transplanted ranged from 110,000 to 412,000. Islet function was assessed by measuring the plasma insulin responses to intravenous glucose and arginine and the plasma glucagon responses to hypoglycemia and arginine. In one patient, islet function was studied during catheterization of the hepatic vein, portal vein, and splenic artery and by analysis of a liver-biopsy specimen. RESULTS: After transplantation, the mean (+/- SD) fasting plasma glucose concentration was 122 +/- 47 mg per deciliter (6.8 +/- 2.6 mmol per liter) and the hemoglobin A1c concentration was 6.0 +/- 0.8 percent in the five patients. The values were most abnormal--214 mg per deciliter (11.9 mmol per liter) and 7.3 percent, respectively--in the patient who received only 110,000 islets. The acute plasma insulin responses to glucose and to arginine in the five patients were 23 +/- 13 and 26 +/- 10 microU per milliliter (168 +/- 94 and 184 +/- 70 pmol per liter), respectively, as compared with 58 +/- 6 and 37 +/- 8 microU per milliliter (416 +/- 44 and 267 +/- 61 pmol per liter) in the normal subjects. The peak plasma glucagon responses to insulin and arginine were 21 +/- 4 and 65 +/- 36 pg per milliliter, respectively, as compared with 125 +/- 28 and 156 +/- 99 pg per milliliter in the normal subjects. All five patients had plasma epinephrine but not pancreatic polypeptide responses to hypoglycemia. The results of the hepatic-vein catheterization in one patient indicated that the transplanted islets released insulin and glucagon in response to arginine. Immunoperoxidase staining of this patient's liver-biopsy specimen showed that the islets contained insulin, glucagon, and somatostatin but not pancreatic polypeptide. CONCLUSIONS: Intrahepatic transplantation of as few as 265,000 islets can result in the release of insulin and glucagon at appropriate times and in prolonged periods of insulin independence.

Adolescent↗

PubMed1992

Selective impairment of neuroendocrine and hemodynamic responses to a mu-opioid peptide in aged rats.

The objective of this study was to determine if there are age-related alterations in hemodynamic and/or neuroendocrine responses to the mu-opioid receptor agonist, [D-Ala2,MePhe4,Gly(ol)5] enkephalin (DAMGO), or corticotropin releasing hormone (CRH) administered centrally. To this end, DAMGO (1-3 nmoles) or CRH (1 nmole) was injected intracerebroventricularly (icv) to freely moving young (6-8 month) and aged (24-26 month) Fischer 344 male rats. Blood pressure, heart rate (HR), and plasma concentrations of norepinephrine (NE), epinephrine (EPI), adrenocorticotropin (ACTH), and prolactin (PRL) were measured over time. Under basal conditions, NE levels were higher and blood pressures were lower in aged rats, whereas there were no significant differences in EPI, ACTH, or PRL levels. The stimulatory effect of DAMGO on blood pressure, HR, and plasma EPI and ACTH was attenuated, but the PRL response was enhanced in aged cohorts. In contrast, there were no age-related differences in the NE responses to DAMGO or CRH nor in CRH-induced increases in EPI or ACTH. The sympathoadrenal and hemodynamic effects of DAMGO were blocked by naloxone in both age groups. These results indicate that alterations in mu-opioid function with age are specific for the opioid system and do not reflect a generalized decline in central regulation of neuroendocrine and cardiovascular function.

Adrenocorticotropic Hormone↗

PubMed1992

Hypertension and insulin resistance: role of sympathetic nervous system activity.

The purpose of this study was to test the hypothesis that heightened sympathetic nervous system (SNS) activity contributes to the mechanism by which hypertension is associated with insulin resistance in humans. We performed frequently sampled intravenous glucose tolerance tests to determine tissue sensitivity to metabolic effects of insulin (SI) and measured plasma norepinephrine (NE) levels in 21 normotensive and 14 hypertensive Caucasian subjects. Compared with the normotensive subjects, hypertensive subjects had decreased SI (5.4 +/- 0.5 vs. 4.0 +/- 0.7 x 10(-5) x min-1 x pM-1; P = 0.03) but similar plasma NE levels (normotensive: 1.82 +/- 0.12 vs. hypertensive: 1.73 +/- 0.16 nM; P = 0.23). In a multiple regression model, only body mass index (BMI) and mean arterial blood pressure (MABP) were significant independent predictors of SI [SI = (-0.513)(BMI) + (-0.058)(MABP) + 23.6; r = 0.748; P = 0.0001]; age, plasma glucose, epinephrine, and NE level did not enter this model. As an additional test of this hypothesis, seven hypertensive subjects were restudied after 10 days of guanadrel therapy to determine whether SI would increase during suppression of SNS activity by guanadrel. Despite a significant reduction in plasma NE levels with guanadrel (baseline: 1.63 +/- 0.18 vs. guanadrel: 0.99 +/- 0.14 nM; P = 0.01), there was no significant change in SI (baseline: 2.97 +/- 0.78 vs. guanadrel: 2.41 +/- 0.54 x 10(-5).min-1 x pM-1; analysis of variance P = 0.57). We conclude that, in the Caucasian population we studied, heightened SNS activity is not essential for the insulin resistance observed in hypertensive humans.

Adult↗

PubMed1992

Glucose turnover and its regulation during intense exercise and recovery in normal male subjects.

Intense exercise to exhaustion is expected to be associated with rapid and large changes in glucose production (Ra) and utilization (Rd). To quantify these, and to determine their mechanisms and those of the prolonged postexercise hyperglycemia, we measured circulating metabolic regulators and glucose kinetics, the latter by the method of enriched tracer [3-3H] glucose infusion during exercise. Eighteen fit, lean young male subjects exercised to exhaustion at 80% of maximal workload (approximately 100% VO2max) on a cycle ergometer. Plasma glucose was 4.90 +/- 0.08 mM/L at rest, increased during exercise, then abruptly to 6.91 +/- 0.40 mM/L at 4 min recovery then gradually declined. Plasma insulin was constant during exercise, then doubled to 162 +/- 28 pmol/l until 20 min recovery, before declining. Plasma glucagon increased by 71 +/- 11 pg/mL. Plasma norepinephrine increased 18-fold and epinephrine 14-fold, both declining by 20 min recovery. Ra increased 7-fold by exhaustion to 13.0 +/- 1.18 mg/kg/min, then decreased to 2.43 +/- 0.24 mg/kg/min by 9 min, then to about 2 mg/kg/min the rest of recovery. Rd rose 3-fold (6.61 +/- 0.70 mg/kg/min), and remained lower than Ra to 7 min recovery, but thereafter declined more slowly. Thus, the rapid and extremely large increase in Ra was not matched by the increment in Rd during exercise and early recovery. We suggest that unlike in exercise of lesser intensity, the major mediators of both the increase in Ra and the restraint of the increase in Rd are the catecholamines. The post exercise hyperglycemia and hyperinsulinemia are appropriate to muscle glycogen repletion.

Adult↗

PubMed1991

Effect of an oral alpha 2-adrenergic blocker (MK-912) on pancreatic islet function in non-insulin-dependent diabetes mellitus.

We used MK-912, a potent new selective alpha 2-adrenergic receptor antagonist that is active orally, to study the effect of short-term, selective alpha 2-blockade on fasting plasma glucose (FPG) and pancreatic islet function in non-insulin-dependent diabetes (NIDDM). Ten asymptomatic patients with NIDDM received either a single oral dose of MK-912 (2 mg) or placebo in a double-blind, cross-over study. B-cell function was measured by the acute insulin response (AIR) to glucose (1.66 mmol/kg intravenously [IV]) and by the AIR to arginine (5 g IV) during a hyperglycemic glucose clamp at a mean glucose level of 32.1 mmol/L to provide an estimation of maximal B-cell secretory capacity. A-cell function was estimated by the acute glucagon response (AGR) to arginine during the glucose clamp. Effective alpha 2-adrenergic blockade was apparently achieved, as there were substantial increases of plasma norepinephrine (NE) (P less than .01) and both systolic blood pressure (SBP) (P less than .01) and diastolic blood pressure (DBP) (P less than .05) after treatment with MK-912, but not after placebo. MK-912 caused a significant (P less than .05) although modest decrease of FPG that was associated with a small increase of fasting plasma insulin (P less than 0.01), C-peptide (P less than .05), and glucagon (P less than .01). FPG and hormone levels remained unchanged after placebo. MK-912 tended to increase the AIR (P = .06) and the C-peptide response (P = .07) to glucose compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1991

Beta-adrenergic regulation of insulin secretion: evidence of tissue heterogeneity of beta-adrenergic responsiveness in the elderly.

Aging is associated with reduced beta-adrenergic receptor (beta-AR) function in several tissues. If this age effect on beta-ARs also applies to the pancreatic B-cell, it would result in relatively unopposed alpha-adrenergic inhibition of insulin secretion with adrenergic stimulation during stress states. This study compared insulin secretory responses to beta-AR stimulation (multiple IV doses of isoproterenol) with cardiac and circulating mononuclear lymphocyte (MNL) beta-AR responses in 9 healthy, non-obese young subjects, and 9 healthy, non-obese old subjects. We found no age-related decrease in the relationship between isoproterenol dose and insulin response. In contrast, the old subjects had significantly reduced heart rate responses to isoproterenol and generally lower MNL beta-AR function. We conclude that pancreatic B-cell beta-AR mediated function is not impaired in the elderly, suggesting that heterogeneity of tissue beta-AR mediated function exists in this population. Diminished pancreatic islet beta-AR mediated function does not appear to be a mechanism that predisposes healthy older individuals to the development of stress hyperglycemia.

Adult↗

PubMed1991

Regulation of venous alpha-adrenergic responses in older humans.

Decreased adrenergic responsiveness in human aging could be a result of downregulation mediated by the age-related increase in sympathetic nervous system (SNS) tone. If so, suppression of SNS tone in elderly subjects should upregulate adrenergic responsiveness into the range observed for younger subjects. To test this hypothesis, we examined alpha 1 (phenylephrine)- and alpha 2 (clonidine)-adrenergic agonist-mediated venoconstriction in a group of 15 older healthy subjects (age 59-73 yr) during placebo and when SNS tone was suppressed by guanadrel (15 mg twice daily for 3 wk). During guanadrel compared with placebo 1) there were decreases in plasma norepinephrine (NE) levels (1.47 +/- 0.07 to 0.80 +/- 0.06 nM; P less than 0.001) and in the extravascular NE release rate derived from [3H]NE kinetics (11.8 +/- 1.4 to 6.1 +/- 1.0 nmol.min-1.m-2; P = 0.01), suggesting suppression of SNS tone; 2) there was an augmented clonidine-mediated venoconstriction response [analysis of variance (ANOVA) P = 0.01]; and 3) there was no detectable change in phenylephrine-mediated venoconstriction (ANOVA P = 0.60). When compared with previous results from young subjects, maximal alpha 2-adrenergic venoconstriction during guanadrel was decreased in the elderly compared with the young, although their response appeared to be appropriately upregulated by the decrease in SNS tone. The lack of an age-related decrease in alpha 1-adrenergic venoconstriction, together with the lack of upregulation of this response during guanadrel, suggests that regulation of this alpha 1-adrenergic response is impaired in the older group.

Aged↗

PubMed1991

Effect of desipramine on norepinephrine metabolism in humans: interaction with aging.

To determine whether differences in neuronal reuptake contribute to age-related changes of sympathetic nervous system activity, we compared norepinephrine (NE) release and metabolism during [3H]NE infusion and decay in six young (age 19-26 yr) and seven older (age 61-73 yr) healthy nonobese subjects. Subjects were studied on a control day and on a separate day after desipramine (DMI; 125 mg orally), a neuronal reuptake blocker. Compartmental analysis of plasma NE specific activity was used to determine several NE kinetic parameters. Plasma NE levels and NE spillover rates were higher in the elderly. Although plasma NE was unaffected by DMI in both age groups, both the metabolic clearance rate of NE from plasma and the rate of NE spillover into plasma fell in young and older groups during DMI. Furthermore, DMI dramatically lowered the mass of NE in the extravascular compartment and the rate of NE entry into the extravascular compartment. Thus neuronal uptake blockade has major effects on NE release as well as NE metabolism in humans. However, age-related differences in NE kinetics cannot be explained by differences in neuronal uptake.

Adult↗

PubMed1991

Glucoregulatory and hormonal responses to repeated bouts of intense exercise in normal male subjects.

Glucose turnover and its regulation were studied during and after two identical bouts of intense exhaustive exercise separated by 1 h to define differences in response. Six lean young postabsorptive male subjects exercised at approximately 100% maximal O2 uptake (3.7 +/- 0.3 l/min) for 13.0 +/- 0.7 min for the first (EX1) and 13.2 +/- 0.8 min for the second (EX2) bout. Plasma glucose increased during EX1 and peaked at 7.0 +/- 0.6 mmol/l in early recovery but to 5.8 +/- 0.5 mmol/l (P less than 0.05) after EX2, and both the hyperglycemic and the hyperinsulinemic responses were less after EX2 (P less than 0.015, analysis of variance). The hyperglycemia was due to lesser increments in glucose utilization (Rd) (3-fold resting) than glucose production (Ra) (7-fold) toward exhaustion and for 7 min of recovery. The rise in Rd was more rapid (P less than 0.05) and metabolic clearance rate was greater during (P = 0.015) and from 9 to 60 min after EX2, and Ra also remained higher during recovery (P less than 0.05). Marked and similar increments in plasma norepinephrine (18-fold) and epinephrine (14-fold) occurred with both bouts. Plasma glucagon increments were small and not different. Therefore, 1) more circulating glucose was used with EX2, 2) greater metabolic clearance rate during and after EX2 suggests local muscle adaptations due to EX1, and 3) significant correlations (P less than 0.002) between plasma norepinephrine and Ra (r = 0.82) and Ra - Rd (r = 0.52) and between epinephrine and Ra (r = 0.71) and Ra - Rd (r = 0.48) suggest a major regulatory role for the catecholamine responses.

Adult↗

PubMed1991

Importance of hepatic glucoreceptors in sympathoadrenal response to hypoglycemia.

To ascertain whether hepatic glucoreceptors are important to hypoglycemic counterregulation, a localized euglycemic clamp was employed across the liver during general hypoglycemia. Dogs were infused peripherally with insulin (18-21 pmol.kg-1.min-1) for 150 min to induce systemic hypoglycemia. During the liver-clamp (LC) protocol, glucose was infused via the portal vein to maintain euglycemia at the liver. In control experiments, i.e., matched infusion (MI), glucose was infused peripherally at a rate determined to yield similar arterial glycemia levels in the two protocols. Arterial glucose concentrations were not different between protocols during the final hour of insulin infusion (3.26 +/- 0.21 and 3.25 +/- 0.21 mM during LC and MI, respectively; P = 0.91). Calculated hepatic glucose concentrations during the same period were significantly higher for LC (5.22 +/- 0.23 mM) than for MI (3.25 +/- 0.21 mM). During MI, both epinephrine and norepinephrine rose significantly from basal values of 562 +/- 87 pM and 1.21 +/- 0.19 nM to plateaus of 3691 +/- 1097 pM (P = 0.0001) and 2.38 +/- 0.35 nM (P = 0.0002), respectively. However, during LC, the elevation in epinephrine was suppressed by 42 +/- 8% (P = 0.015) relative to MI. Six of seven animals demonstrated a suppression in the norepinephrine response, averaging 32 +/- 13% (NS, P = 0.068). The glucagon response to hypoglycemia was unaffected by the level of hepatic glycemia. Hepatic hypoglycemia is essential to produce the full sympathoadrenal response to insulin-induced hypoglycemia.

Adrenal Glands↗

PubMed1991

Effect of epinephrine on pancreatic beta-cell and alpha-cell function in patients with NIDDM.

The purposes of this study were to determine whether patients with non-insulin-dependent diabetes mellitus (NIDDM) have an enhanced glycemic response to epinephrine (EPI) and to quantitate the effect of physiological elevations of EPI on pancreatic islet function in these patients. The increment of plasma glucose (PG) in response to 45 min of EPI infusion (mean plasma EPI 2490 pM) was more than twofold greater in nine NIDDM patients than in 20 nondiabetic control subjects (mean +/- SE delta PG 3.9 +/- 0.3 vs. 1.7 +/- 0.1 mM, P less than 0.0001). The effects of EPI on beta-cell and alpha-cell function were compared in nine NIDDM patients and 9 age- and weight-matched control subjects during infusions of saline or two doses of EPI on separate days (mean plasma EPI 270, 1120, and 2490 pM). On each day, the acute insulin response (AIR) and acute glucagon response (AGR) to 5 g i.v. arginine were measured at three matched steady-state PG levels (means of 9, 14, and 29 mM). Beta-Cell sensitivity to glucose (slope of glucose potentiation) and beta-cell secretory capacity, or AIRmax (AIR at the highest clamped PG level), were calculated. In control subjects, EPI inhibited the AIR at PG concentrations of 9 and 14 mM (both P less than 0.05) but had no effect on the AIRmax, resulting in a rightward shift of the curve relating the AIR and PG and a decrease in the slope of glucose potentiation (P less than 0.01). In contrast in NIDDM patients, EPI inhibited the AIR at all PG levels, including the AIRmax (all P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1990

Beta-adrenergic blockade decreases norepinephrine release in humans.

Beta-Adrenergic blockade with propranolol (PRP) has been reported to cause an increase in plasma norepinephrine (NE) levels in humans, which suggests that a reflex increase in sympathetic nervous system (SNS) vasoconstrictor tone compensates for the hypotensive effect of beta-adrenergic blockade. However, plasma NE levels are an indirect measure of SNS activity. We have developed a two-compartment model of NE kinetics to estimate NE release into an extravascular compartment as a more comprehensive measure of systemic SNS activity. To determine whether beta-adrenergic blockade alters extravascular NE release, we studied nine healthy subjects during sequential infusions of saline and PRP. During PRP infusion, there was an increase in plasma NE levels [1.03 +/- 0.13 to 1.27 +/- 0.21 (SE) nM; P = 0.05], but the extravascular NE release rate decreased significantly (15.5 +/- 1.6 to 9.2 +/- 1.2 nmol.min-1.m-2, P = 0.0002). The plasma NE concentration increased despite the fall in extravascular NE release rate primarily because the clearance of NE from plasma declined (1.55 +/- 0.08 to 1.18 +/- 0.07 l.min-1.m-2, P = 0.0001); the NE spillover rate into plasma did not change (1.73 +/- 0.18 to 1.75 +/- 0.23 nmol.min-1.m-2, P = 0.89). We conclude that PRP decreases extravascular NE release in humans. Suppression of SNS activity may be an additional mechanism of action of nonselective beta-adrenergic antagonists in humans.

Adult↗