Insulin Secretion and Clearance after Subacute Estradiol Administration in Postmenopausal Women

Abstract Context: Data from large clinical trials of postmenopausal women suggest that the incidence of diabetes is reduced in women randomized to estrogen-based hormone therapy when compared with placebo. Whether this is due to an effect of estrogen on insulin or glucose metabolism remains unclear. Objective: Our objective was to test the hypothesis that estradiol (E2) increases insulin secretion and clearance. Design: Serum insulin and C-peptide (CPEP) responses to hyperglycemia (250 mg/dl) plus iv l-arginine were measured on 2 separate days, with (EST) and without [control (CON)] subacute (24 h) transdermal E2 administration. Study Participants: There were 11 postmenopausal women (mean ± sd; 55 ± 4 yr) included in this study. Main Outcomes: Insulin secretion and clearance were estimated from the CPEP area under the curve and the molar ratio of CPEP to insulin area under the curve, respectively. Mean glucose disposal rate (GDR) was estimated from the rate of glucose infusion during the final 30 min of the hyperglycemic clamp. Results: There were no differences in insulin secretion or clearance between the EST and CON days. Fasting glucose was lower on the EST compared with the CON (93 ± 6 vs. 98 ± 8 mg/dl), but mean GDR was not different. However, when one outlier was excluded from analysis, GDR was increased after EST compared with CON. Furthermore, a strong inverse association was observed between years since menopause and E2-mediated changes in GDR (r = −0.794; P = 0.004). Conclusions: Contrary to our hypothesis, 24-h transdermal E2 administration did not alter insulin secretion or clearance in postmenopausal women. However, a longer time since menopause was associated with a reduced effect of E2 to increase glucose uptake.

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Effects of treadmill exercise to exhaustion on the insulin response to hyperglycemia in untrained men

Journal of Applied Physiology ◽

10.1152/jappl.1991.70.1.246 ◽

1991 ◽

Vol 70 (1) ◽

pp. 246-250 ◽

Cited By ~ 15

Author(s):

J. P. Kirwan ◽

R. E. Bourey ◽

W. M. Kohrt ◽

M. A. Staten ◽

J. O. Holloszy

Keyword(s):

Insulin Secretion ◽

Early Phase ◽

Pancreatic Beta Cell ◽

Late Phase ◽

Insulin Response ◽

Creatine Kinase Activity ◽

Whole Body ◽

Glucose Disposal ◽

C Peptide ◽

Hyperglycemic Clamp

The effects of a single bout of exercise to exhaustion on pancreatic insulin secretion were determined in seven untrained men by use of a 3-h hyperglycemic clamp with plasma glucose maintained at 180 mg/100 ml. Clamps were performed either 12 h after an intermittent treadmill run at approximately 77% maximum O2 consumption or without prior exercise. Arterialized blood samples for glucose, insulin, and C-peptide determination were obtained from a heated hand vein. The peak insulin response during the early phase (0–10 min) of the postexercise clamp was higher (81 +/- 8 vs. 59 +/- 9 microU/ml; P less than 0.05) than in the nonexercise clamp. Incremental areas under the insulin (376 +/- 33 vs. 245 +/- 51 microU.ml-1.min) and C-peptide (17 +/- 2 vs. 12 +/- 1 ng.ml-1.min) curves were also greater (P less than 0.05) during the early phase of the postexercise clamp. No differences were observed in either insulin concentrations or whole body glucose disposal during the late phase (15–180 min). Area under the C-peptide curve was greater during the late phase of the postexercise clamp (650 +/- 53 vs. 536 +/- 76 ng.ml-1.min, P less than 0.05). The exercise bout induced muscle soreness and caused an elevation in plasma creatine kinase activity (142 +/- 32 vs. 305 +/- 31 IU/l; P less than 0.05) before the postexercise clamp. We conclude that in untrained men a bout of running to exhaustion increased pancreatic beta-cell insulin secretion during the early phase of the hyperglycemic clamp. Increased insulin secretion during the late phase of the clamp appeared to be compensated by increased insulin clearance.

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Insulin secretion-independent effects of GLP-1 on canine liver glucose metabolism do not involve portal vein GLP-1 receptors

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00121.2005 ◽

2005 ◽

Vol 289 (5) ◽

pp. G806-G814 ◽

Cited By ~ 37

Author(s):

Dominique Dardevet ◽

Mary Courtney Moore ◽

Catherine A. DiCostanzo ◽

Ben Farmer ◽

Doss W. Neal ◽

...

Keyword(s):

Insulin Secretion ◽

Portal Vein ◽

Glucose Disposal ◽

Control Group ◽

Oral Glucose ◽

Oral Glucose Tolerance Testing ◽

Hyperglycemic Clamp ◽

Independent Effects ◽

Hepatic Portal

Whether glucagon-like peptide (GLP)-1 requires the hepatic portal vein to elicit its insulin secretion-independent effects on glucose disposal in vivo was assessed in conscious dogs using tracer and arteriovenous difference techniques. In study 1, six conscious overnight-fasted dogs underwent oral glucose tolerance testing (OGTT) to determine target GLP-1 concentrations during clamp studies. Peak arterial and portal values during OGTT ranged from 23 to 65 pM and from 46 to 113 pM, respectively. In study 2, we conducted hyperinsulinemic-hyperglycemic clamp experiments consisting of three periods (P1, P2, and P3) during which somatostatin, glucagon, insulin and glucose were infused. The control group received saline, the PePe group received GLP-1 (1 pmol·kg−1·min−1) peripherally, the PePo group received GLP-1 (1 pmol·kg−1·min−1) peripherally (P2) and then intraportally (P3), and the PeHa group received GLP-1 (1 pmol·kg−1·min−1) peripherally (P2) and then through the hepatic artery (P3) to increase the hepatic GLP-1 load to the same extent as in P3 in the PePo group ( n = 8 dogs/group). Arterial GLP-1 levels increased similarly in all groups during P2 (∼50 pM), whereas portal GLP-1 levels were significantly increased (2-fold) in the PePo vs. PePe and PeHa groups during P3. During P2, net hepatic glucose uptake (NHGU) increased slightly but not significantly (vs. P1) in all groups. During P3, GLP-1 increased NHGU in the PePo and PeHa groups more than in the control and PePe groups (change of 10.8 ± 1.3 and 10.6 ± 1.0 vs. 5.7 ± 1.0 and 5.4 ± 0.8 μmol·kg−1·min−1, respectively, P < 0.05). In conclusion, physiological GLP-1 levels increase glucose disposal in the liver, and this effect does not involve GLP-1 receptors located in the portal vein.

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Effects of eccentric exercise on insulin secretion and action in humans

Journal of Applied Physiology ◽

10.1152/jappl.1993.75.5.2151 ◽

1993 ◽

Vol 75 (5) ◽

pp. 2151-2156 ◽

Cited By ~ 19

Author(s):

D. S. King ◽

T. L. Feltmeyer ◽

P. J. Baldus ◽

R. L. Sharp ◽

J. Nespor

Keyword(s):

Insulin Secretion ◽

Eccentric Exercise ◽

Plasma Glucose ◽

Early Phase ◽

Pancreatic Beta Cell ◽

Late Phase ◽

Insulin Response ◽

Whole Body ◽

Glucose Disposal ◽

Hyperglycemic Clamp

The effects of an exhaustive bout of eccentric exercise on insulin secretion and action were determined using the hyperglycemic clamp technique. Clamps were performed on eight healthy men after 7 days of inactivity and approximately 36 h after a bout of eccentric exercise. Eccentric exercise consisted of 10 sets of 10 repetitions of combined knee extensions and flexions for each leg at a mean torque 84 +/- 5% of peak concentric torque. During the hyperglycemic clamp procedure, plasma glucose concentration was acutely raised to 10 mmol/l and was maintained near this level for 120 min. Arterialized blood samples were obtained from a heated hand vein to determine plasma glucose and insulin concentrations. Eccentric exercise appeared to produce marked muscle damage, as indicated by a 50-fold increase in plasma creatine phosphokinase (100 +/- 17 vs. 5,209 +/- 3,811 U/l, P < 0.001) and subjective reports of muscle soreness. Peak insulin response during the early phase (0–10 min) of the hyperglycemic clamp was higher after eccentric exercise (183 +/- 38 microU/ml) than after the control clamp (100 +/- 23 microU/ml, P < 0.005). Late-phase (10- to 120-min) insulin response was not altered after eccentric exercise. Peak plasma C-peptide concentrations were higher during the early phase (5.0 +/- 0.7 vs. 4.3 +/- 0.8 ng/ml, P < 0.05) and the late phase (7.5 +/- 0.9 vs. 5.4 +/- 0.6 ng/ml, P < 0.05). Prior eccentric exercise had no significant effect on whole body glucose disposal or glucose disposal rate adjusted for prevailing plasma insulin concentration. These data provide evidence that a single bout of eccentric exercise causes an increase in pancreatic beta-cell insulin secretion in response to hyperglycemia.

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PACAP stimulates insulin secretion but inhibits insulin sensitivity in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1998.274.5.e834 ◽

1998 ◽

Vol 274 (5) ◽

pp. E834-E842 ◽

Cited By ~ 16

Author(s):

Karin Filipsson ◽

Giovanni Pacini ◽

Anton J. W. Scheurink ◽

Bo Ahrén

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Elimination Rate ◽

Insulin Response ◽

Area Under The Curve ◽

Glucose Disposal ◽

Sensitivity Index ◽

Maximal Effect ◽

Intravenous Glucose

Although pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates insulin secretion, its net influence on glucose homeostasis in vivo has not been established. We therefore examined the action of PACAP-27 and PACAP-38 on insulin secretion, insulin sensitivity, and glucose disposal as derived from the minimal model of glucose disappearance during an intravenous glucose tolerance test in anesthetized mice. PACAP-27 and PACAP-38 markedly and equipotently potentiated glucose-stimulated insulin secretion, with a half-maximal effect at 33 pmol/kg. After PACAP-27 or PACAP-38 (1.3 nmol/kg), the acute (1–5 min) insulin response was 3.8 ± 0.4 nmol/l (PACAP-27) and 3.3 ± 0.3 nmol/l (PACAP-38), respectively, vs. 1.4 ± 0.1 nmol/l after glucose alone ( P < 0.001), and the total area under the curve for insulin (AUCinsulin) was potentiated by 60% ( P < 0.001). In contrast, PACAP-27 and PACAP-38 reduced the insulin sensitivity index (SI) [0.23 ± 0.04 10−4min−1/(pmol/l) for PACAP-27 and 0.29 ± 0.06 10−4min−1/(pmol/l) for PACAP-38 vs. 0.46 ± 0.02 10−4min−1/(pmol/l) for controls ( P < 0.01)]. Furthermore, PACAP-27 or PACAP-38 did not affect glucose elimination determined as glucose half-time or the glucose elimination rate after glucose injection or the area under the curve for glucose. Moreover, glucose effectiveness and the global disposition index (AUCinsulin times SI) were not affected by PACAP-27 or PACAP-38. Finally, when given together with glucose, PACAP-27 did not alter plasma glucagon or norepinephrine levels but significantly increased plasma epinephrine levels. We conclude that PACAP, besides its marked stimulation of insulin secretion, also inhibits insulin sensitivity in mice, the latter possibly explained by increased epinephrine. This complex action explains why the peptide does not enhance glucose disposal.

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Abnormal regulation of HGP by hyperglycemia in mice with a disrupted glucokinase allele

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1997.273.4.e743 ◽

1997 ◽

Vol 273 (4) ◽

pp. E743-E750 ◽

Cited By ~ 10

Author(s):

Luciano Rossetti ◽

Wei Chen ◽

Meizhu Hu ◽

Meredith Hawkins ◽

Nir Barzilai ◽

...

Keyword(s):

Insulin Secretion ◽

Hepatic Glucose Production ◽

Glucose Production ◽

Glucose Disposal ◽

Relative Role ◽

Β Cells ◽

Plasma Insulin Concentration ◽

Hyperglycemic Clamp ◽

Human Diabetes ◽

Hepatic Glucose

Glucokinase (GK) catalyzes the phosphorylation of glucose in β-cells and hepatocytes, and mutations in the GK gene have been implicated in a form of human diabetes. To investigate the relative role of partial deficiencies in the hepatic vs. pancreatic GK activity, we examined insulin secretion, glucose disposal, and hepatic glucose production (HGP) in response to hyperglycemia in transgenic mice 1) with one disrupted GK allele, which manifest decreased GK activity in both liver and β-cells (GK+/−), and 2) with decreased GK activity selectively in β-cells (RIP-GKRZ). Liver GK activity was decreased by 35–50% in the GK+/− but not in the RIP-GKRZ compared with wild type (WT) mice. Hyperglycemic clamp studies were performed in conscious mice with or without concomitant pancreatic clamp. In all studies [3-3H]glucose was infused to measure the rate of appearance of glucose and HGP during 80 min of euglycemia (Glc ∼5 mM) followed by 90 min of hyperglycemia (Glc ∼17 mM). During hyperglycemic clamp studies, steady-state plasma insulin concentration, rate of glucose infusion, and rate of glucose disappearance (Rd) were decreased in both GK+/− and RIP-GKRZ compared with WT mice. However, whereas the basal HGP (at euglycemia) averaged ∼22 mg ⋅ kg−1 ⋅ min−1in all groups, during hyperglycemia HGP was suppressed by only 48% in GK+/− compared with ∼70 and 65% in the WT and RIP-GKRZ mice, respectively. During the pancreatic clamp studies, the ability of hyperglycemia per se to increase Rd was similar in all groups. However, hyperglycemia inhibited HGP by only 12% in GK+/−, vs. 42 and 45%, respectively, in the WT and RIP-GKRZ mice. We conclude that, although impaired glucose-induced insulin secretion is common to both models of decreased pancreatic GK activity, the marked impairment in the ability of hyperglycemia to inhibit HGP is due to the specific decrease in hepatic GK activity.

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Fiber intake predicts ghrelin levels in overweight and obese postmenopausal women

Acta Endocrinologica ◽

10.1530/eje-09-0018 ◽

2009 ◽

Vol 161 (1) ◽

pp. 65-72 ◽

Cited By ~ 8

Author(s):

David H St-Pierre ◽

Rémi Rabasa-Lhoret ◽

Marie-Ève Lavoie ◽

Antony D Karelis ◽

Irene Strychar ◽

...

Keyword(s):

Total Energy ◽

Postmenopausal Women ◽

Hormonal Regulation ◽

Eating Habits ◽

Area Under The Curve ◽

Glucose Disposal ◽

Fiber Intake ◽

Euglycemic Hyperinsulinemic Clamp ◽

Fiber Consumption ◽

The Impact

BackgroundGhrelin levels are decreased upon food intake, but the impact of specific diet-derived macronutrients on its regulation remains unclear. In addition, because of ghrelin's association with body weight regulation, it is important to understand the mechanisms regulating its levels in obese individuals.ObjectiveTo examine the effect of specific macronutrients on ghrelin levels in overweight and obese postmenopausal women.MethodsThirty-five subjects underwent a euglycemic/hyperinsulinemic clamp (EHC) to examine glucose disposal and total ghrelin (TotG) and acylated ghrelin (AG) levels. Macronutrient intake was evaluated with a 3-day food questionnaire.ResultsUnder fasting conditions, positive associations were observed between fiber intake and TotG and AG levels. Fasting AG also correlated positively with the intake of total energy, as well as monounsaturated and polyunsaturated lipids. Importantly, fiber consumption explained up to 26 and 23% of the variation in TotG and AG respectively. During the EHC, TotG levels were significantly reduced at all times, while AG was decreased at 60 min only. TotG area under the curve (AUC) values were positively associated with fiber and polyunsaturated lipid intake, while AG AUC values correlated positively with fiber, total energy, carbohydrate, and lipid intake. Interestingly, fiber intake explained up to 21% of the variation in TotG AUC, while total energy intake predicted up to 21% of the variation in the AG AUC.ConclusionThe present study suggests that fiber intake is an important regulator of ghrelin levels both in fasting and in hyperinsulinemic conditions. Overall, these results reinforce the importance of the intimate association between eating habits and gastrointestinal hormonal regulation.

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Sex Hormone–Binding Globulin and Risk of Clinical Diabetes in American Black, Hispanic, and Asian/Pacific Islander Postmenopausal Women

Clinical Chemistry ◽

10.1373/clinchem.2012.193086 ◽

2012 ◽

Vol 58 (10) ◽

pp. 1457-1466 ◽

Cited By ~ 21

Author(s):

Brian H Chen ◽

Kathleen Brennan ◽

Atsushi Goto ◽

Yiqing Song ◽

Najib Aziz ◽

...

Keyword(s):

Postmenopausal Women ◽

Diabetes Risk ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Clinical Diabetes ◽

Total Testosterone ◽

Inverse Association ◽

Hormone Binding ◽

Strong Inverse Association ◽

Asian Pacific

Abstract BACKGROUND Recent prospective studies have shown a strong inverse association between sex hormone–binding globulin (SHBG) concentrations and risk of clinical diabetes in white individuals. However, it remains unclear whether this relationship extends to other racial/ethnic populations. METHODS We evaluated the association between baseline concentrations of SHBG and clinical diabetes risk in the Women's Health Initiative Observational Study. Over a median follow-up of 5.9 years, we identified 642 postmenopausal women who developed clinical diabetes (380 blacks, 157 Hispanics, 105 Asians) and 1286 matched controls (777 blacks, 307 Hispanics, 202 Asians). RESULTS Higher concentrations of SHBG at baseline were associated with a significantly lower risk of clinical diabetes [relative risk (RR), 0.15; 95% CI, 0.09–0.26 for highest vs lowest quartile of SHBG, adjusted for BMI and known diabetes risk factors]. The associations remained consistent within ethnic groups [RR, 0.19 (95% CI, 0.10–0.38) for blacks; RR, 0.17 (95% CI, 0.05–0.57) for Hispanics; and 0.13 (95% CI, 0.03–0.48) for Asians]. Adjustment for potential confounders, such as total testosterone (RR, 0.11; 95% CI, 0.07–0.19) or HOMA-IR (RR, 0.26; 95% CI, 0.14–0.48) did not alter the RR substantially. In addition, SHBG concentrations were significantly associated with risk of clinical diabetes across categories of hormone therapy use (never users: RRper SD = 0.42, 95% CI, 0.34–0.51; past users: RRper SD = 0.53;, 95% CI, 0.37–0.77; current users: RRper SD = 0.57; 95% CI, 0.46–0.69; P-interaction = 0.10). CONCLUSIONS In this prospective study of postmenopausal women, we observed a robust, inverse relationship between serum concentrations of SHBG and risk of clinical diabetes in American blacks, Hispanics, and Asians/Pacific Islanders. These associations appeared to be independent of sex hormone concentrations, adiposity, or insulin resistance.

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Effects of physiologic and supraphysiologic hyperglycemia on early and late-phase insulin secretion in chronically dialyzed uremic patients

Acta Endocrinologica ◽

10.1530/acta.0.1210251 ◽

1989 ◽

Vol 121 (2) ◽

pp. 251-258 ◽

Cited By ~ 8

Author(s):

Ole Schmitz

Keyword(s):

Insulin Secretion ◽

Beta Cell ◽

Serum Insulin ◽

Late Phase ◽

Insulin Response ◽

Glucose Disposal ◽

Insulin Resistant ◽

Normal Glucose ◽

Glucose Challenge ◽

Uremic Patients

Abstract. To test secretory capacity of the beta-cell to a glucose stimulus in uremic patients on chronic dialysis, three hyperglycemic clamps (plasma glucose increments: 1, 4.5 and 11 mmol/l) were performed in 8 uremic and 8 healthy subjects. Early-phase insulin and C-peptide responses (ΔI and ΔC) during the initial 6 min were consistently exaggerated at all three steps in uremic patients compared with controls (ΔI. 16 ± 4 vs 4 ± 2, 41 ± 11 vs 15 ± 4 and 60 ± 12 vs 24 ± 5 mU/l; ΔC. 0.39 ± 0.13 vs 0.07 ± 0.02, 0.40 ± 0.13 vs 0.16 ± 0.02 and 0.73 ± 0.15 vs 0.29 ± 0.04 nmol/l, p < 0.05 in all cases). Similarly, late-phase insulin secretion defined as the insulin increment between 90 and 120 min after initiation of the glucose challenge was enhanced in uremic patients at the two highest glycemic steps (44 ± 10 vs 16 ± 2 and 123 ± 29 vs 44 ± 5 mU/l, both p < 0.01). The raised late-phase insulin response allowed comparable glucose disposal in the two groups (uremic patients: 9.2 ± 1.0 and 15.5 ± 1.6 mg · kg−1 · min−1· Controls: 9.0 ± 1.3 and 19.9 ± 2.4 mg · kg−1 · min−1). The slopes of potentiation, i.e. the slopes of the regression lines expressing the relationship between changes in insulin increments and changes in glucose, were markedly steeper in uremic patients (0.45 ± 0.09 and 0.66 ± 0.20, early and late-phase respectively) than in controls (0.20 ± 0.06 and 0.25 ± 0.03). No relationship between serum insulin responses and electrolytes or PTH was demonstrated. In conclusion, despite several factors which may inhibit the ability of the beta-cell to respond to a glucose stimulus, acute hyperglycemia elicits in insulin-resistant uremic subjects an exaggerated early and late-phase insulin secretion which is able to compensate for insulin resistance, thereby maintaining normal glucose disposal.

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A reduced incretin effect mediated by the rs7903146 variant in the TCF7L2 Gene is an early marker of beta-cell dysfunction in obese youth

10.2337/figshare.12665477 ◽

2020 ◽

Author(s):

Alfonso Galderisi ◽

Domenico Trico ◽

Bridget Pierpont ◽

Veronika Shabanova ◽

Stephanie Samuels ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Beta Cell ◽

Plasma Glucose ◽

Metabolic Phenotype ◽

Glucose Disposal ◽

Incretin Effect ◽

Tcf7l2 Gene ◽

Intravenous Glucose ◽

Hyperglycemic Clamp

Background. The risk genotype for the common variant rs7903146 of the transcription factor-7-like-2 gene (TCF7L2) has been found to affect the incretin response in healthy and obese adults, however, whether a similar functional defect is also present in obese adolescents remains unexplored. Herein, we examined the functional effect of the rs7903146 variant in the TCF7L2 gene on the incretin effect and determined its translational metabolic manifestation by performing deep phenotyping of the incretin system, beta-cell function relative to insulin sensitivity, the Gastrointestinal Induced Glucose Disposal (GIGD) in obese youths with normal and impaired glucose tolerance. Methods Thirty nine non-diabetic obese adolescents (15[14,18] years; BMI 37[33, 43]kg/m2) were genotyped for the rs7903146 of TCF7L2 and underwent a 3-hour OGTT followed by an iso-glycemic intravenous glucose infusion (iso-IVGTT) to match the plasma glucose concentrations during the OGTT and a hyperglycemic clamp with arginine stimulation. The incretin effect was measured as 100*(AUC-SROGTT – AUC-SRiso-IVGTT)/AUC-SROGTT [AUC-SR=AUC of C-peptide secretion rate]. Participants were grouped into tertiles according to the percentage incretin effect (High-, Moderate- and Low-incretin effect) to describe their metabolic phenotype. Results The presence of T risk allele for TCF7L2 was associated with a markedly reduced incretin effect compared to the wild type genotype(0.3[-7.2,14] vs 37.8[12.5-52.4], p<0.002) When the cohort was stratified by incretin effect, the High-, Moderate- and Low-incretin groups did not differ with respect to anthropometric features, while the Low-incretin group exhibited higher 1-h glucose (p=0.015), a reduced disposition index, insulin sensitivity and insulin clearance, compared with the High-incretin group. Gastrointestinal induced glucose disposal (GIGD) was reduced in the Low-incretin group (p=0.001). The three groups did not differ with respect to intravenous glucose-induced insulin secretion and arginine response during the hyperglycemic clamp. Conclusion A reduced incretin effect and its association with the TCF7L2 variant rs7903146 identify an early metabolic phenotype in obese non-diabetic youths, featured by a higher plasma glucose peak at 1hr, lower insulin secretion, sensitivity and clearance, and gastrointestinal glucose disposal.

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Effects of growth hormone releasing hormone on insulin action and insulin secretion in a hypopituitary patient evaluated by the clamp technique

Acta Endocrinologica ◽

10.1530/acta.0.1270093 ◽

1992 ◽

Vol 127 (1) ◽

pp. 93-96 ◽

Cited By ~ 3

Author(s):

Silva Arslanian ◽

Satish Kalhan

Keyword(s):

Growth Hormone ◽

Insulin Secretion ◽

Insulin Action ◽

Glucose Disposal ◽

Second Phase ◽

Growth Hormone Releasing Hormone ◽

Releasing Hormone ◽

Euglycemic Clamp ◽

Hyperglycemic Clamp ◽

Hyperinsulinemic Euglycemic Clamp

The effect of growth hormone releasing hormone (GHRH-44) therapy on insulin action and secretion was evaluated in a hypopituitary patient after one month and one year of treatment. Hepatic and peripheral insulin action was studied with the hyperinsulinemic-euglycemic clamp in combination with [6,6-2H2]glucose tracer infusion. First and second phase insulin secretion was assessed with the hyperglycemic clamp. Prior to GHRH-44 therapy the hypopituitary patient had higher insulin mediated glucose disposal rate and lower basal and stimulated insulin concentrations by more than two standard deviations from the mean of a control group. Following therapy there was no change in basal hepatic glucose production; however, there was evidence of diminished peripheral insulin action. This was manifested by decreased insulin mediated glucose disposal during the hyperinsulinemic-euglycemic clamp, and increased insulin secretion during the hyperglycemic clamp. We conclude that GHRH-44 therapy in this patient was associated with decreased peripheral insulin action which was compensated for by increased insulin secretion.

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