Demonstration of a role for growth hormone in glucose counterregulation

Feo, Pierpaolo De; Perriello, G.; Torlone, Elisabetta; Ventura, M. M.; Santeusanio, Fausto; Brunetti, P; Gerich, John E.; Bolli, Geremia B.

doi:10.1152/ajpendo.1989.256.6.e835

Cited by 68 publications

(63 citation statements)

References 19 publications

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“…Insulin resistance is of primary importance to avoid hypoglycemia in periods where glucose usage should be reduced, such as fasting, exercise, and stress; and energy requirements could be overtaken by lipolysis. Although glucagon and catecholamines are of predominant importance, an adequate response to hypoglycemia during treatment of diabetes presumes also a preserved GH secretion (3,4).…”

Section: Introductionmentioning

confidence: 99%

Prevalence of diabetes mellitus in 6050 hypopituitary patients with adult-onset GH deficiency before GH replacement: a KIMS analysis

Abs¹,

Mattsson²,

Thunander³

et al. 2013

European Journal of Endocrinology

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Objective: GH deficiency (GHD) in adults is characterized by a tendency toward obesity and an adverse body composition with visceral fat deposit and may thus predispose to the development of type 2 diabetes mellitus. The aim of this study was to assess the observed prevalence proportion (PP) and observed PP over expected PP ratio (standardized prevalence proportion ratio, SPR) of diabetes according to International Diabetes Federation criteria in a large cohort of GH-untreated adult-onset GHD patients. Design and methods: Associations between baseline variables and diabetes prevalence in 6050 GHD patients from KIMS (Pfizer International Metabolic Database) were studied and robust Poisson-regression analyses were performed. Comparisons between baseline status and HbA1c categories in the nondiabetic patients were done with covariance analysis. P values !0.05 were considered statistically significant. Results: PP was 9.3% compared with the expected 8.2%. SPR was 1.13 (95% confidence intervals (95% CIs), 1.04-1.23), which was significantly increased in females (1.23; 95% CI, 1.09-1.38%) but not in males (SPR 1.04; 95% CI, 0.92-1.17%). PP increased significantly by age, familial diabetes, country selection, BMI, waist circumference, number of pituitary deficiencies, and GHD etiology. SPR decreased significantly by age and increased significantly by BMI, waist circumference, and IGF1 SDS. Multiple regression model showed that the most important impact on SPR was from age and BMI. HbA1c values of 6.0-6.5% were found in 9.5% of nondiabetic patients and were associated with higher BMI and waist circumference. Conclusions: GHD is associated with an increased prevalence of diabetes, largely to be explained by the adverse body composition. These data urge toward early initiation of lifestyle modification measures.

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Section: Introductionmentioning

confidence: 99%

Prevalence of diabetes mellitus in 6050 hypopituitary patients with adult-onset GH deficiency before GH replacement: a KIMS analysis

Abs¹,

Mattsson²,

Thunander³

et al. 2013

European Journal of Endocrinology

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“…Therefore, ghrelin secretion might be triggered by an acute decrease of plasma glucose concentrations. The hypoglycemia alarm symptom of hunger and the responses of GH and cortisol play an important role in the defense against insulin-induced hypoglycemia (10,11). Ghrelin might act, at least in part, as a physiological mediator of these protective mechanisms.…”

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confidence: 99%

Ghrelin Is Not Necessary for Adequate Hormonal Counterregulation of Insulin-Induced Hypoglycemia

et al. 2002

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Ghrelin is a novel enteric hormone that stimulates growth hormone (GH), ACTH, and epinephrine; augments plasma glucose; and increases food intake by inducing the feeling of hunger. These characteristics make ghrelin a potential counterregulatory hormone. At present, it is not known whether ghrelin increases in response to insulin-induced hypoglycemia. To answer this question, we compared plasma ghrelin concentrations after a short-term insulin infusion that was allowed or not (euglycemic clamp) to cause hypoglycemia (2.7 ؎ 0.2 mmol/l at 30 min) in five healthy volunteers. In both studies, plasma ghrelin concentrations decreased (P < 0.01) after insulin infusion (hypoglycemia by 14%, euglycemia by 22%), reached a nadir at 30 min, and returned to baseline at 60 min, without differences between the hypoglycemia and the euglycemia studies. Glucagon, cortisol, and GH increased in response to hypoglycemia despite the decreased ghrelin. There was a strong correlation (R 2 ‫؍‬ 0.91, P < 0.002) between the insulin sensitivity of the subjects and the percentage suppression of ghrelin from baseline. These data demonstrate that ghrelin is not required for the hormonal defenses against insulin-induced hypoglycemia and that insulin can suppress ghrelin levels in healthy humans. These results raise the possibility that postprandial hyperinsulinemia is responsible for the reduction of plasma ghrelin that occurs during meal intake. Diabetes 51:2911-2914, 2002 G hrelin, a 28 -amino acid hormone, was recently identified in the stomach as the endogenous ligand for the growth hormone (GH) secretagogue receptor (1). Ghrelin is a potent stimulator of GH secretion (2); promotes ACTH, cortisol (2,3), and epinephrine (3) release; increases food intake, possibly by augmenting hypothalamic mRNA levels of neuropeptide Y and agouti gene-related protein (4); and increases plasma glucose in normal subjects (5). Recently, it was shown in humans that circulating ghrelin levels rise shortly before and fall shortly after every meal (6,7) and that ghrelin administration increases subjective hunger and voluntary food intake (8). All of these data suggest that ghrelin works as a hormone signaling the need to conserve energy (9). Therefore, ghrelin secretion might be triggered by an acute decrease of plasma glucose concentrations. The hypoglycemia alarm symptom of hunger and the responses of GH and cortisol play an important role in the defense against insulin-induced hypoglycemia (10,11). Ghrelin might act, at least in part, as a physiological mediator of these protective mechanisms. In addition, ghrelin could directly contribute to glucose counterregulation by stimulating hepatic glucose production. The prompt increase of plasma glucose after an intravenous bolus of ghrelin in healthy humans suggests a direct glycogenolytic activity (5), whereas recent data show that ghrelin upregulates markers of gluconeogenesis and downregulates markers of glycogen synthesis in hepatoma cells (12).For demonstrating that ghrelin is required for glucose counterregul...

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“…It is also possible that growth hormone contributed to the glycaemia-increasing effect of sprinting, at least in the hypoglycaemic group. This is because growth hormone increased above basal levels in response to sprinting and because this hormone has been reported to increase glucose Ra and acutely inhibit glucose Rd in nondiabetic individuals [37]. However, in opposition to this interpretation, glucose Rd has been shown not to fall in response to growth hormone in insulin-treated individuals with type 1 diabetes [38].…”

Section: Discussionmentioning

confidence: 99%

Antecedent hypoglycaemia does not diminish the glycaemia-increasing effect and glucoregulatory responses of a 10 s sprint in people with type 1 diabetes

et al. 2014

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Aims/hypothesis A 10 s sprint has been reported to provide a means to prevent acute post-exercise hypoglycaemia in young adults with type 1 diabetes because of its glycaemia-raising effect, but it is unclear whether this effect is impaired by antecedent hypoglycaemia. The purpose of this study was to investigate whether antecedent hypoglycaemia impairs the glycaemia-raising effect of a 10 s sprint in individuals with type 1 diabetes. Methods Eight individuals underwent a hyperinsulinaemichypoglycaemic or hyperinsulinaemic-euglycaemic clamp on two separate mornings. Thereafter, the participants underwent a basal insulin-euglycaemic clamp before performing a 10 s sprint on a cycle ergometer. The levels of blood glucose and glucoregulatory hormones and rates of glucose appearance (Ra) and disappearance (Rd) were compared between conditions. Results During the morning clamps, blood glucose levels were significantly different between conditions of hypoglycaemia (2.8 ± 0.1 mmol/l) and euglycaemia (5.4 ± 0.2 mmol/l; p < 0.001). Mean glycaemia prior to sprinting was similar (5.6 ± 0.4 and 5.5± 0.3 mmol/l for hypoglycaemic and euglycaemic conditions, respectively; p=0.83). In response to the afternoon sprint, the pattern of increase in blood glucose levels did not differ between conditions, reaching similar maximal levels 45 min after exercise (6.5±0.4 and 6.6±0.3 mmol/l, respectively; p= 0.43). The early post-exercise patterns in glucose Ra and Rd and increases in plasma adrenaline (epinephrine), growth hormone and cortisol levels did not differ between conditions. Conclusions/interpretation Hypoglycaemia in the morning does not diminish the glycaemia-raising effect of an afternoon 10 s sprint in young adults with type 1 diabetes, suggesting that sprinting is a useful strategy for opposing hypoglycaemia, regardless of prior hypoglycaemia.

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Demonstration of a role for growth hormone in glucose counterregulation

Cited by 68 publications

References 19 publications

Prevalence of diabetes mellitus in 6050 hypopituitary patients with adult-onset GH deficiency before GH replacement: a KIMS analysis

Prevalence of diabetes mellitus in 6050 hypopituitary patients with adult-onset GH deficiency before GH replacement: a KIMS analysis

Ghrelin Is Not Necessary for Adequate Hormonal Counterregulation of Insulin-Induced Hypoglycemia

Antecedent hypoglycaemia does not diminish the glycaemia-increasing effect and glucoregulatory responses of a 10 s sprint in people with type 1 diabetes

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