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Examining the effects of hyperglycemia on pancreatic endocrine function in humans: evidence for in vivo glucotoxicity.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2012 Dec; Vol. 97 (12), pp. 4682-91. Date of Electronic Publication: 2012 Oct 05. - Publication Year :
- 2012
-
Abstract
- Context: Investigating the impact of hyperglycemia on pancreatic endocrine function promotes our understanding of the pathophysiology of hyperglycemia-related disease.<br />Objective: The objective of the study was to test the hypothesis that experimental hyperglycemia impairs insulin and glucagon secretion.<br />Design: A randomized, crossover in healthy controls, compared with type 2 diabetic patients.<br />Setting: The study was conducted at a university hospital.<br />Participants: Normal glucose-tolerant subjects (n = 10) and patients with type 2 diabetes (n = 10), individually matched by age, sex, and body mass index.<br />Interventions: Normal glucose-tolerant subjects underwent 24 h of experimental hyperglycemia (+5.4 mm above basal). Subjects with type 2 diabetes did not undergo an intervention.<br />Main Outcome Measures: Insulin secretion, glucagon secretion, insulin sensitivity, disposition index, and endogenous glucose production (via [6,6-(2)H(2)]glucose infusion) were measured during hyperglycemic clamps combined with infusion of glucagon-like peptide (GLP)-1(7-36) (0.5 pmol/kg · min) and injection of arginine (5 g).<br />Results: Insulin secretion was correlated with glucagon suppression in subjects with normal glucose tolerance only. Individuals with type 2 diabetes had lower insulin sensitivity (-33 ± 11%) and insulin secretory responses to glucose, GLP-1, and arginine (-40 ± 11, -58 ± 7, and -36 ± 13%, respectively) and higher plasma glucagon and endogenous glucose production compared with normal glucose-tolerant subjects (all P < 0.05). After 24 h of experimental hyperglycemia, insulin sensitivity (-29 ± 10%), disposition index (-24 ± 16%), and GLP-1- (-19 ± 7%) and arginine-stimulated (-15 ± 10%) insulin secretion were decreased in normal glucose-tolerant subjects (all P < 0.05). However, plasma glucagon responses were not affected. Furthermore, experimental hyperglycemia abolished the correlation between insulin secretion and glucagon suppression.<br />Conclusions: Experimental hyperglycemia impaired pancreatic β-cell function but did not acutely impair α-cell glucagon secretion in normal glucose-tolerant subjects.
- Subjects :
- Blood Glucose drug effects
Cross-Over Studies
Diabetes Mellitus, Type 2 blood
Diabetes Mellitus, Type 2 complications
Diabetes Mellitus, Type 2 physiopathology
Female
Glucagon blood
Glucagon metabolism
Glucose Clamp Technique methods
Humans
Hyperglycemia metabolism
Insulin blood
Insulin metabolism
Insulin Secretion
Islets of Langerhans metabolism
Male
Middle Aged
Pancreatic Hormones metabolism
Glucose toxicity
Hyperglycemia physiopathology
Islets of Langerhans drug effects
Islets of Langerhans physiopathology
Pancreatic Hormones physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7197
- Volume :
- 97
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 23043193
- Full Text :
- https://doi.org/10.1210/jc.2012-2097