The effect of age and glycemic level on the response of the beta-cell to glucose-dependent insulinotropic polypeptide and peripheral tissue sensitivity to endogenously released insulin.
(1998)
Journal - The Journal of clinical endocrinology and metabolism (UNITED STATES )
Abstract :
Normal aging is characterized by a progressive impairment in glucose tolerance. An important mechanism underlying the glucose intolerance of aging is an impairment in glucose-induced insulin release. These studies were conducted to determine whether the age-related impairment in insulin release was caused by a decreased beta-cell sensitivity to glucose-dependent insulinotropic polypeptide (GIP). Thirty-one Caucasian men were divided into four groups: two young groups (age range: 19-26 yr, n = 15) and two old groups (age range: 67-79 yr, n = 16). Each volunteer participated in three studies (n = 93 clamps). Hyperglycemic clamps were conducted at two doses [basal plasma glucose (G) + 5.4 mmol/L and G + 12.8 mmol/L] for 120 min. In the initial hyperglycemic clamp, only glucose was infused. In subsequent studies, GIP was infused at a final rate of 2 or 4 pmol/ kg(-1) x min(-1) from 60-120 min. Basal plasma insulin and GIP levels were similar in the young (41 +/- 6 and 51 +/- 6 pmol/L) and the old subjects (42 +/- 6 and 66 +/- 12 pmol/L) in all studies. First- and second-phase insulin responses were similar during the control study and during the first 60 min of each GIP infusion study in both groups. The 90-120 min GIP values were similar between groups and between hyperglycemic plateaus during the 2 and 4 pmol/kg(-1) x min(-1) GIP infusion (young: 342 +/- 28 and 601 +/- 44 pmol/L, old: 387 +/- 45 and 568 +/- 49 pmol/L). In response to the GIP infusions, significant increases in insulin occurred in young and old at both glucose levels (P < 0.01). The potentiation of the insulin response caused by GIP was greater in the young subjects than in the old, in the G + 5.4 mmol/L studies (P < 0.05). However, the insulin response to GIP was similar in both young and old during the G + 12.8 mmol/L clamps. The insulinotropic effect of the incretin was higher in the young and in the old, in the G + 12.8 mmol clamps, than in the G + 5.4 mmol/L clamps. We conclude that normal aging is characterized by a decreased beta-cell sensitivity to GIP during modest hyperglycemia, which may explain, in part, the age-related impairment in glucose-induced insulin release. We also find that the insulinotropic effect of GIP is increased with increasing levels of hyperglycemia.
| ISSN : | 0021-972X |
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| Mesh Heading : | Adult Aged Aging Blood Glucose Gastric Inhibitory Polypeptide Glucagon Glucose Clamp Technique Humans Insulin Islets of Langerhans Kinetics Male Metabolic Clearance Rate administration & dosage blood blood blood secretion |
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| Mesh Heading Relevant : | physiology metabolism pharmacology secretion drug effects |
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Somatostatin enhances insulin-mediated glucose disposal in elderly subjects.
(1988)
Journal - The Journal of clinical endocrinology and metabolism (UNITED STATES )
Abstract :
Somatostatin (SRIH) infusion has been widely used in metabolic studies of carbohydrate metabolism. While the effects of SRIH itself on various aspects of carbohydrate economy have been assessed in young adults, such studies have not been conducted in the elderly, which represent an increasingly important study group. To examine the effect of SRIH on insulin-mediated glucose disposal in the elderly, we studied 12 (7 men and 5 women) healthy nonobese subjects, aged 65-80 yr. Paired 3-h euglycemic insulin clamp studies were performed in random order employing insulin alone (22 mU/m2.min) or insulin with SRIH (250 micrograms/h) and glucagon (0.4 ng/kg.min) to maintain normal basal plasma glucagon levels. Basal plasma insulin, glucose, glucagon, GH, and glucose production and disappearance were similar on each occasion. Steady state (10-180 min) mean plasma insulin [insulin alone, 298 +/- 12 (+/- SE); insulin; glucagon, and SRIH, 304 +/- 15 pmol/L] and glucagon (insulin alone, 85 +/- 7; insulin, glucagon, and SRIH, 96 +/- 9 ng/L) concentrations were similar. At steady state (150-180 min) glucose production was suppressed to similar levels (insulin alone, 26 +/- 7; insulin, glucagon, and SRIH, 36 +/- 13 mumol/kg.min). However, steady state glucose disposal was significantly higher during the SRIH infusion (insulin alone, 295 +/- 26; insulin, glucagon, and SRIH, 346 +/- 32 mumol/kg.min; P less than 0.02). We conclude that SRIH augments insulin-mediated glucose disposal in healthy older subjects at physiological levels of insulin.
| ISSN : | 0021-972X |
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| Mesh Heading : | Age Factors Aged Aged, 80 and over Drug Synergism Female Glucose Humans Insulin Male Somatostatin |
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| Mesh Heading Relevant : | pharmacokinetics pharmacology pharmacology |
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