The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man.
Open accessAbstract
Sequential determinations of glucose outflow and inflow, and rates of gluconeogenesis from alanine, before, during and after insulin-induced hypoglycemia were obtained in relation to alterations in circulating epinephrine, norepinephrine, glucagon, cortisol, and growth hormone in six normal subjects. Insulin decreased the mean (+/-SEM) plasma glucose from 89+/-3 to 39+/-2 mg/dl 25 min after injection, but this decline ceased despite serum insulin levels of 153+/-22 mul/ml. Before insulin, glucose inflow and outflow were constant averaging 125.3+/-7.1 mg/kg per h. 15 min after insulin, mean glucose outflow increased threefold, but then decreased at 25 min, reaching a rate 15% less than the preinsulin rate. Glucose inflow decreased 80% 15 min after insulin, but increased at 25 min, reaching a maximum of twice the basal rate. Gluconeogenesis from alanine decreased 68% 15 min after insulin, but returned to preinsulin rates at 25 min, and remained constant for the next 25 min, after which it increased linearly. A fourfold increase in mean plasma epinephrine was found 20 min after insulin, with maximal levels 50 times basal. Plasma norepinephrine concentrations first increased significantly at 25 min after insulin, whereas significantly increased levels of cortisol and glucagon occurred at 30 min, and growth hormone at 40 min after insulin. Thus, insulin-induced hypoglycemia in man results from both a decrease in glucose production and an increase in glucose utilization. Accelerated glycogenolysis produced much of the initial, posthypoglycemic increment in glucose production. The contribution of glycogenolysis decreased with time, while that of gluconeogenesis from alanine increased. Of the hormones studied, only the increments in plasma catecholamines preceded or coincided with the measured increase in glucose production after hypoglycemia. It therefore seems probable that adrenergic mechanisms play a major role in the initiation of counter-regulatory responses to insulin-induced hypoglycemia in man.
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Glucose recovery is not due solely to dissipation of insulin.
“Glucose recovery is not due solely to dissipation of insulin.”
From Epinephrine supports the postabsorptive plasma glucose concentration and prevents hypoglycemia when glucagon secretion is deficient in man (1984) · cites this paper as [1]
Epinephrine compensates largely for deficient glucagon secretion.
“Glucagon plays a primary counterregulatory role; epinephrine compensates largely for deficient glucagon secretion.”
From Epinephrine supports the postabsorptive plasma glucose concentration and prevents hypoglycemia when glucagon secretion is deficient in man (1984) · cites this paper as [1]
Glucagon plays a primary counterregulatory role.
“Glucagon plays a primary counterregulatory role; epinephrine compensates largely for deficient glucagon secretion.”
From Epinephrine supports the postabsorptive plasma glucose concentration and prevents hypoglycemia when glucagon secretion is deficient in man (1984) · cites this paper as [1]
The principles of hypoglycemic glucose counterregulation and those of nonhypoglycemic glucose counterregulation in both the postprandial and postabsorptive states are fundamentally the same.
“Thus, the principles of hypoglycemic glucose counterregulation (1-7) and those of nonhypoglycemic glucose counterregulation in both the postprandial (8, 9) and the postabsorptive states are fundamentally the same.”
From Epinephrine supports the postabsorptive plasma glucose concentration and prevents hypoglycemia when glucagon secretion is deficient in man (1984) · cites this paper as [1]
Glucose recovery fails to occur only in the absence of both glucagon and epinephrine.
“Glucose recovery fails to occur only in the absence of both glucagon and epinephrine.”
From Epinephrine supports the postabsorptive plasma glucose concentration and prevents hypoglycemia when glucagon secretion is deficient in man (1984) · cites this paper as [1]
In both hypoglycemic glucose counterregulation and another model of nonhypoglycemic glucose counterregulation, adrenomedullary epinephrine, but not sympathetic neural norepinephrine, compensates for deficient glucagon secretion.
“Second, in both hypoglycemic glucose counterregulation (1-7) and in another model of nonhypoglycemic glucose counterregulation (9), adrenomedullary epinephrine, but not sympathetic neural norepinephrine, compensates for deficient glucagon secretion.”
From Epinephrine supports the postabsorptive plasma glucose concentration and prevents hypoglycemia when glucagon secretion is deficient in man (1984) · cites this paper as [1]
Plasma epinephrine concentrations of >400 pg/ml occur during heavy exercise and absolute hypoglycemia, as well as during a variety of acute illnesses.
“As noted earlier, plasma epinephrine concentrations of this magnitude do occur during heavy exercise and absolute hypoglycemia, as well as during a variety of acute illnesses.”
From Epinephrine plasma metabolic clearance rates and physiologic thresholds for metabolic and hemodynamic actions in man. (1980) · cites this paper as [28]
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Self-citation
- Authors
- Garber, A. J., Cryer, P. E., Santiago, J. V., Haymond, M. W., Pagliara, A. S., & Kipnis, D. M.
- Affiliations
- Howard Hughes Medical Institute (US)
- ORCID
- Haymond, M W
- Venue
- Journal of Clinical Investigation
- Published
- 1976-07-01
- Volume
- 58
- Issue
- 1
- Pages
- 7-15
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC333149
- OpenAlex
- W2151836253
- Cited by
- 351
- References
- 7
- Citations by year
- 2025: 3 · 2024: 1 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 2
- FWCI
- 17.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- insulin-induced hypoglycemia, counterregulatory response, adrenergic mechanisms, epinephrine, norepinephrine, glucagon, cortisol, growth hormone, gluconeogenesis, alanine, glycogenolysis, glucose production, glucose utilization, catecholamines
- MeSH terms
- Adrenergic alpha-Agonists, Adult, Alanine, Epinephrine, Glucagon, Gluconeogenesis, Glucose, Humans, Hydrocortisone, Hypoglycemia, Insulin, Kinetics, Male, Norepinephrine, Radioisotope Dilution Technique, Growth Hormone, Sympathetic Nervous System
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