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Differing physiological effects of epinephrine in type 1 diabetes and nondiabetic humans.
Am J Physiol Endocrinol Metab. 2005 Jan; 288(1):E178-86.AJ

Abstract

Acute increases of the key counterregulatory hormone epinephrine can be modified by a number of physiological and pathological conditions in type 1 diabetic patients (T1DM). However, it is undecided whether the physiological effects of epinephrine are also reduced in T1DM. Therefore, the aim of this study was to determine whether target organ (liver, muscle, adipose tissue, pancreas, cardiovascular) responses to epinephrine differ between healthy subjects and T1DM patients. Thirty-four age- and weight-matched T1DM (n = 17) and healthy subjects (n = 17) underwent two randomized, single-blind, 2-h hyperinsulinemic euglycemic clamp studies with (Epi) and without epinephrine infusion. Muscle biopsy was performed at the end of each study. Epinephrine levels during Epi were similar in all groups (4,039 +/- 384 pmol/l). Glucose (5.3 +/- 0.06 mmol/l) and insulin levels (462 +/- 18 pmol/l) were also similar in all groups during the glucose clamps. Glucagon responses to Epi were absent in T1DM and significantly reduced compared with healthy subjects. Endogenous glucose production during the final 30 min was significantly greater during Epi in healthy subjects compared with T1DM (8.4 +/- 1.3 vs. 4.4 +/- 0.6 micromol.kg(-1).min(-1), P = 0.041). Glucose uptake showed almost a twofold greater decrease with Epi in healthy subjects vs. T1DM (Delta31 +/- 2 vs. Delta17 +/- 2 nmol.kg(-1).min(-1), respectively, P = 0.026). Glycerol, beta-hydroxybutyrate, and nonesterified fatty acid (NEFA) all increased significantly more in T1DM compared with healthy subjects. Increases in systolic blood pressure were greater in healthy subjects, but reductions of diastolic blood pressure were greater in T1DM patients with Epi. Reduction of glycogen synthase was significantly greater during epinephrine infusion in T1DM vs. healthy subjects. In summary, despite equivalent epinephrine, insulin, and glucose levels, changes in glucose flux, glucagon, and cardiovascular responses were greater in healthy subjects compared with T1DM. However, T1DM patients had greater lipolytic responses (glycerol and NEFA) during Epi. Thus we conclude that there is a spectrum of significant in vivo physiological differences of epinephrine action at the liver, muscle, adipose tissue, pancreas, and cardiovascular system between T1DM and healthy subjects.

Authors+Show Affiliations

Guy DA
Division of Pediatric Endocrinology, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232-6303, USA.
Sandoval D
No affiliation info available
Richardson MA
No affiliation info available
Tate D
No affiliation info available
Flakoll PJ
No affiliation info available
Davis SN
No affiliation info available

MeSH

AdultAutonomic Nervous SystemBiopsyBlood GlucoseBlood PressureCalorimetry, IndirectDiabetes Mellitus, Type 1EpinephrineFemaleGlucagonGlucose Clamp TechniqueHeart RateHuman Growth HormoneHumansHydrocortisoneInsulinMaleMuscle, SkeletalNorepinephrinePancreatic PolypeptideSympathomimetics

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15585598

Citation

Guy, Deanna Aftab, et al. "Differing Physiological Effects of Epinephrine in Type 1 Diabetes and Nondiabetic Humans." American Journal of Physiology. Endocrinology and Metabolism, vol. 288, no. 1, 2005, pp. E178-86.
Guy DA, Sandoval D, Richardson MA, et al. Differing physiological effects of epinephrine in type 1 diabetes and nondiabetic humans. Am J Physiol Endocrinol Metab. 2005;288(1):E178-86.
Guy, D. A., Sandoval, D., Richardson, M. A., Tate, D., Flakoll, P. J., & Davis, S. N. (2005). Differing physiological effects of epinephrine in type 1 diabetes and nondiabetic humans. American Journal of Physiology. Endocrinology and Metabolism, 288(1), E178-86.
Guy DA, et al. Differing Physiological Effects of Epinephrine in Type 1 Diabetes and Nondiabetic Humans. Am J Physiol Endocrinol Metab. 2005;288(1):E178-86. PubMed PMID: 15585598.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differing physiological effects of epinephrine in type 1 diabetes and nondiabetic humans. AU - Guy,Deanna Aftab, AU - Sandoval,Darleen, AU - Richardson,M A, AU - Tate,Donna, AU - Flakoll,Paul J, AU - Davis,Stephen N, PY - 2004/12/9/pubmed PY - 2005/3/3/medline PY - 2004/12/9/entrez SP - E178 EP - 86 JF - American journal of physiology. Endocrinology and metabolism JO - Am J Physiol Endocrinol Metab VL - 288 IS - 1 N2 - Acute increases of the key counterregulatory hormone epinephrine can be modified by a number of physiological and pathological conditions in type 1 diabetic patients (T1DM). However, it is undecided whether the physiological effects of epinephrine are also reduced in T1DM. Therefore, the aim of this study was to determine whether target organ (liver, muscle, adipose tissue, pancreas, cardiovascular) responses to epinephrine differ between healthy subjects and T1DM patients. Thirty-four age- and weight-matched T1DM (n = 17) and healthy subjects (n = 17) underwent two randomized, single-blind, 2-h hyperinsulinemic euglycemic clamp studies with (Epi) and without epinephrine infusion. Muscle biopsy was performed at the end of each study. Epinephrine levels during Epi were similar in all groups (4,039 +/- 384 pmol/l). Glucose (5.3 +/- 0.06 mmol/l) and insulin levels (462 +/- 18 pmol/l) were also similar in all groups during the glucose clamps. Glucagon responses to Epi were absent in T1DM and significantly reduced compared with healthy subjects. Endogenous glucose production during the final 30 min was significantly greater during Epi in healthy subjects compared with T1DM (8.4 +/- 1.3 vs. 4.4 +/- 0.6 micromol.kg(-1).min(-1), P = 0.041). Glucose uptake showed almost a twofold greater decrease with Epi in healthy subjects vs. T1DM (Delta31 +/- 2 vs. Delta17 +/- 2 nmol.kg(-1).min(-1), respectively, P = 0.026). Glycerol, beta-hydroxybutyrate, and nonesterified fatty acid (NEFA) all increased significantly more in T1DM compared with healthy subjects. Increases in systolic blood pressure were greater in healthy subjects, but reductions of diastolic blood pressure were greater in T1DM patients with Epi. Reduction of glycogen synthase was significantly greater during epinephrine infusion in T1DM vs. healthy subjects. In summary, despite equivalent epinephrine, insulin, and glucose levels, changes in glucose flux, glucagon, and cardiovascular responses were greater in healthy subjects compared with T1DM. However, T1DM patients had greater lipolytic responses (glycerol and NEFA) during Epi. Thus we conclude that there is a spectrum of significant in vivo physiological differences of epinephrine action at the liver, muscle, adipose tissue, pancreas, and cardiovascular system between T1DM and healthy subjects. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/15585598/Differing_physiological_effects_of_epinephrine_in_type_1_diabetes_and_nondiabetic_humans_ DB - PRIME DP - Unbound Medicine ER -