ACUTE EFFECTS OF EXOGENOUS GROWTH HORMONE IN MAN: TIME- AND DOSE-BOUND MODIFICATION OF GLUCOSE TOLERANCE AND GLUCOSE-INDUCED INSULIN RELEASE

1975 ◽  
Vol 80 (2) ◽  
pp. 247-261 ◽  
Author(s):  
Ulf Adamson ◽  
Erol Cerasi
Keyword(s):  
Growth Hormone ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Insulin Release ◽  
Pancreatic Beta Cells ◽  
Chronic Administration ◽  
Major Influence ◽  
Insulinogenic Index ◽  
Significant Deterioration ◽  
K Value

ABSTRACT The time and dose dependency of the effects of a 30-min long iv infusion of human growth hormone (GH) on glucose tolerance and glucose-stimulated insulin release was investigated in 19 healthy subjects. Glucose tolerance deteriorated immediately following GH, and the k-value continued to decrease up to 300 min later. A small but significant reduction of glucose tolerance persisted 24 h after GH administration. Significant deterioration of glucose tolerance was observed with the smallest GH dose used (5 μg per kg body weight), increasing the amount of the hormone having no further major influence. Glucose-stimulated insulin release was significantly inhibited 1 h after administration of a relatively high GH dose (40 μg per kg), both if expressed as mean plasma insulin levels, or as insulin release per magnitude of glucose stimulation (insulinogenic index). In the majority of subjects, insulin release was inhibited also by lower GH doses (5–20 μg GH per kg). However, the mean change with these doses was not statistically significant. The inhibitory effect of GH on insulin secretion seemed to have a duration of several hours. Five hours, but not 24 h, after GH administration (10 μg GH per kg) insulin release was still significantly suppressed. It is suggested that the initial effect of GH on pancreatic beta cells may be inhibition of insulin release, in contrast with the enhancement of insulin secretion observed during chronic administration of GH.

DIMINISHED SENSITIVITY OF THE INSULIN RESPONSE TO GLUCOSE FOLLOWING GROWTH HORMONE INFUSION IN MAN

1976 ◽  
Vol 81 (4) ◽  
pp. 735-742 ◽  
Author(s):  
Ulf Adamson ◽  
Erol Cerasi
Keyword(s):  
Growth Hormone ◽  
Blood Glucose ◽  
Insulin Release ◽  
Dose Response ◽  
Plasma Insulin ◽  
Insulin Dose ◽  
Insulin Response ◽  
Insulinogenic Index ◽  
K Value ◽  
Insulin Response To Glucose

ABSTRACT The acute effect of growth hormone (GH) administration on the dose-kinetics of glucose-stimulated insulin release was investigated in eight healthy, non-obese male subjects. The glucose-insulin dose-response relationship in these subjects was established by performing glucose infusions at three different dose levels. In a second series of experiments, the glucose infusions were preceded by a 30 min infusion of GH (40 μg/kg body weight), terminated 60 min before administration of glucose. GH induced small but significant reductions in the basal levels of blood glucose and plasma insulin. The glucose tolerance (k-value) was diminished after GH at all glucose doses. Both the initial late phases of insulin response to glucose were impaired following GH treatment. This effect was most pronounced when the intermediary glucose dose (eliciting a blood glucose level around 300 mg/100 ml) was used. Thus, the insulinogenic index (whole period of stimulation) was reduced by GH to 88.9 ± 7.6, 60.4 ± 7.1 and 74.3 ± 11.0% of the respective controls when the smallest, the intermediate, and the largest glucose loads, respectively, were given. The blood glucose-plasma insulin dose-response curves were shifted to the right of the control ones when glucose infusion was preceded by GH. These findings suggest that GH diminishes the sensitivity of the islet for the insulin releasing action of glucose. Some possible mechanisms by which GH may modify insulin release are discussed.

Loss of growth hormone signaling in the mouse germline or in adulthood reduces islet mass and alters islet function with notable sex differences

2021 ◽  
Author(s):  
Silvana Duran-Ortiz ◽  
Kathryn L. Corbin ◽  
Ishrat Jahan ◽  
Nicholas B. Whitticar ◽  
Sarah E Morris ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Body Fat ◽  
Isolated Islets ◽  
Wild Type ◽  
Cross Sectional ◽  
Islet Mass ◽  
The Impact

In the endocrine pancreas, growth hormone (GH) is known to promote pancreatic islet growth and insulin secretion. In this study, we show that GH receptor (GHR) loss in the germline and in adulthood impacts islet mass in general but more profoundly in male mice. GHR knockout (GHRKO) mice have enhanced insulin sensitivity and low circulating insulin. We show that the total cross-sectional area of isolated islets (estimated islet mass) was reduced by 72% in male but by only 29% in female GHRKO mice compared to wild type controls. Also, islets from GHRKO mice secreted ~50% less glucose-stimulated insulin compared to size-matched islets from wild type mice. We next used mice with a floxed Ghr gene to knock down the GHR in adult mice at six-months of age (6mGHRKO) and examined the impact on glucose and islet metabolism. By 12-months of age, female 6mGHRKO mice had increased body fat and reduced islet mass but had no change in glucose tolerance or insulin sensitivity. However, male 6mGHRKO mice had nearly twice as much body fat, substantially reduced islet mass, and enhanced insulin sensitivity, but no change in glucose tolerance. Despite large losses in islet mass, glucose-stimulated insulin secretion from isolated islets was not significantly different between male 6mGHRKO and controls while isolated islets from female 6mGHRKO mice showed increased glucose-stimulated insulin release. Our findings demonstrate the importance of GH to islet mass throughout life and that unique sex-specific adaptations to the loss of GH signaling allow mice to maintain normal glucose metabolism.

scholarly journals Sustained Decrease of Early-Phase Insulin Secretion in Japanese Women with Gestational Diabetes Mellitus who Developed Impaired Glucose Tolerance and Impaired Fasting Glucose Postpartum

2015 ◽  
Vol 6 ◽  
pp. JCM.S32743 ◽  
Author(s):  
Hiroko Katayama ◽  
Daisuke Tachibana ◽  
Akihiro Hamuro ◽  
Takuya Misugi ◽  
Koka Motoyama ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Plasma Glucose Level ◽  
Fasting Glucose ◽  
Japanese Women ◽  
Insulinogenic Index ◽  
Model Assessment ◽  
Homeostasis Model Assessment

Objective The aim of this study was to compare glucose intolerance in the antenatal and the postpartum periods using a 75-g oral glucose tolerance test (OGTT) in the Japanese women with gestational diabetes mellitus (GDM) using a retrospective design. Patients and Methods Data were obtained from 85 Japanese women with GDM who delivered from April 2011 through April 2015 and who underwent an OGTT 6–14 weeks postpartum. The women were divided into two groups based on the results of the postpartum OGTT: one group with normal glucose tolerance (NGT) and the other with impaired glucose tolerance (IGT) as well as impaired fasting glucose (IFG). We analyzed the associations between postpartum IGT–IFG and various factors. Results Antenatally, a significant difference was observed between the groups only in the 1-hour plasma glucose level of the 75-g OGTT. Postpartum results of plasma glucose level were significantly higher at 0.5, 1, and 2 hours in the IGT–IFG group than those in the NGT group. Moreover, a significant decrease in the levels of 0.5-hour immunoreactive insulin and insulinogenic index was observed in the IGT–IFG group compared to those in the NGT group. Homeostasis model assessment-insulin resistance and homeostasis model assessment β-cell function of both groups were found to significantly decrease in the postpartum period; however, there was no significant change in the insulinogenic index of either group. Conclusions Our study clearly showed that the postpartum IGT and IFG levels of Japanese women with GDM are affected by impaired early-phase insulin secretion; however, insulin resistance promptly improves.

Glucose Tolerance and Insulin Secretion in Children before and during Recombinant Growth Hormone Treatment

1998 ◽  
Vol 50 (1) ◽  
pp. 32-37 ◽  
Author(s):  
Guido Filler ◽  
Peter Amendt ◽  
Klaus-Dieter Kohnert ◽  
Siegmar Devaux ◽  
Jochen H.H. Ehrich
Keyword(s):  
Growth Hormone ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Growth Hormone Treatment ◽  
Hormone Treatment ◽  
Recombinant Growth Hormone

scholarly journals MON-215 Clinical Factors Associated with Insulin Secretion and Sensitivity in Patients with Primary Aldosteronism

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Yuya Tsurutani ◽  
Sho Katsuragawa ◽  
Tomoko Takiguchi ◽  
Jun Saito ◽  
Masao Omura ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Multiple Regression ◽  
Potassium Level ◽  
Insulinogenic Index ◽  
Clinical Variables ◽  
Impaired Insulin ◽  
Matsuda Index ◽  
Positive Correlations

Abstract Introduction: Primary aldosteronism (PA) is associated with an increased risk of impaired glucose tolerance or type 2 diabetes mellitus. Previous studies have reported that impaired insulin secretion and insulin sensitivity in PA may lead to impaired glucose tolerance. However, the relationship between PA and glucose tolerance, and the factor associated with these glucose metabolism abnormalities is not well understood. In particular, few studies have analyzed the association between aldosterone excess and insulin sensitivity or resistance after the adjustment for other clinical variables. In this study, we analyzed the associations between multiple clinical variables observed in PA and the indices of insulin sensitivity and resistance, using the result of 75 g oral glucose tolerance test (OGTT).Method: This was a retrospective observational study that analyzed the data of 646 patients with PA who underwent adrenal venous sampling and 75 g OGTT. The insulinogenic index and Matsuda index, indices of insulin secretion and sensitivity, respectively, were calculated from the results of a 75 g OGTT. Correlations between these indices and the multiple clinical variables were analyzed. In addition, we performed multiple regression analyses to identify the independent explanatory variables of these indices.Results: Insulinogenic index had positive correlations with the body mass index (BMI), alanine aminotransferase (ALT) level, triglyceride (TGL) level, and potassium level, and negative correlations with both age and plasma aldosterone concentration (PAC). In a multiple regression analysis, both the age (β = -0.231, p < 0.001) and potassium level (β = 0.175, p = 0.002) were selected as the independent explanatory factors. The Matsuda index had positive correlations with the PAC and cortisol level after a 1 mg dexamethasone suppression test (DST), and negative correlations with BMI, ALT level, TGL level, plasma renin activity (PRA), and potassium level. In a multiple regression analysis, BMI (β = -0.216, p < 0.001), ALT level (β = -0.290, p < 0.001), TGL level (β = -0.225, p < 0.001), the cortisol level after 1 mg DST (β = 0.124, p = 0.009), and PRA (β = -0.119, p = 0.019) were selected as the independent explanatory factors.Conclusion: In PA patients, older age and decreased potassium levels were associated with impaired insulin secretion. An increase in the variables associated with metabolic abnormalities such as BMI, ALT, and TGL were associated with decreased insulin sensitivity. In addition, we found that decreased PRA was associated with increased insulin sensitivity.

scholarly journals Regional Variations of Insulin Secretion and Insulin Sensitivity in Japanese Participants With Normal Glucose Tolerance

2021 ◽  
Vol 8 ◽  
Author(s):  
Kiriko Watanabe ◽  
Moritake Higa ◽  
Yoshimasa Hasegawa ◽  
Akihiro Kudo ◽  
Richard C. Allsopp ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Regional Differences ◽  
Insulin Response ◽  
Normal Glucose Tolerance ◽  
Sensitivity Index ◽  
Insulinogenic Index ◽  
Genetic Traits ◽  
Normal Glucose

Purpose: Regional differences in dietary patterns in Asian countries might affect the balance of insulin response and sensitivity. However, this notion is yet to be validated. To clarify the regional differences in the insulin response and sensitivity and their relationship to nutrients, we compared the insulin secretory response during an oral glucose tolerance test in Japanese participants.Methods: This observational retrospective cohort study analyzed the data from participants with normal glucose tolerance (NGT) from four distinct areas of Japan with regard to the food environment: Fukushima, Nagano, Tokushima, and Okinawa based on data available in the Japanese National Health Insurance database.Results: Although the glucose levels were comparable among the four regions, the insulin responses were significantly different among the regions. This difference was observed even within the same BMI category. The plot between the insulin sensitivity index (Matsuda index) and insulinAUC/glucoseAUC or the insulinogenic index showed hyperbolic relationships with variations in regions. The indices of insulin secretion correlated positively with fat intake and negatively with the intake of fish, carbohydrate calories, and dietary fiber.Conclusions: We found that significant regional differences in insulin response and insulin sensitivity in Japanese participants and that nutritional factors may be linked to these differences independently of body size/adiposity. Insulin response and insulin sensitivity can vary among adult individuals, even within the same race and the same country, and are likely affected by environmental/lifestyle factors as well as genetic traits.

ENHANCEMENT OF INSULIN RELEASE TO ACUTE GLYCAEMIC STIMULATION WITH DEPRESSION OF BASAL INSULIN PRODUCTION RATES IN INSULINOMA FOLLOWING DIAZOXIDE ADMINISTRATION

1970 ◽  
Vol 63 (3) ◽  
pp. 392-404 ◽  
Author(s):  
Richard E. Bailey ◽  
Albert Castro ◽  
Rosanne M. Kramer ◽  
Dorothy Macfarlane
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Insulin Release ◽  
Plasma Insulin ◽  
Insulin Biosynthesis ◽  
Oral Glucose ◽  
Glucose Tolerance Tests ◽  
Tolerance Curve ◽  
Insulinoma Cells ◽  
Secretion Rates

ABSTRACT Single and double load oral glucose tolerance tests were performed repetitively both before and during administration of diazoxide to a 15-year old girl who had an insulin secreting islet cell tumour. Plasma insulin concentrations increased above baseline values by a greater magnitude in response to a single acute oral glycaemic stimulus following diazoxide treatment, compared to the increases resulting from comparable prediazoxide glucose tolerance tests, and plasma insulin either attained higher values or sustained elevations for a longer duration during the early part (first hour) of the single load tests. This provides evidence that diazoxide does not prevent the normal insulin release response to a glycaemic stimulus, and that enhanced insulin secretion rates may occur with insulinomas under the study conditions employed. Fasting plasma insulin concentrations were lower during the period of diazoxide administration which indicates that insulin biosynthesis was depressed under fasting steady-state conditions. Considering that the first part of the glucose tolerance curve reflects primarily insulin release, our data is consistent with the view that insulin storage within the insulinoma cells is preserved under the study conditions employed and may even be enhanced by diazoxide. Consequently, depression of insulin biosynthesis is considered to be a resultant effect and not a primary action of diazoxide. These results suggest a possible basis for »distinguishing« types of insulinomas should additional perspective reveal that glycaemic-induced enhancement of insulin secretion rates cannot be made to occur uniformly in diazoxide treated patients having insulinomas.

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