scholarly journals High prevalence of glucokinase mutations in Italian children with MODY. Influence on glucose tolerance, first-phase insulin response, insulin sensitivity and BMI

Diabetologia ◽  
2001 ◽  
Vol 44 (7) ◽  
pp. 898-905 ◽  
Author(s):  
A. Cuesta-Munoz ◽  
A. Caumo ◽  
F. Cerutti ◽  
S. Toni ◽  
N. Sulli ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Insulin Response ◽  
High Prevalence ◽  
Italian Children ◽  
First Phase Insulin Response ◽  
Glucokinase Mutations

scholarly journals Beneficial Effect of Diazoxide in Obese Hyperinsulinemic Adults1

1998 ◽  
Vol 83 (6) ◽  
pp. 1911-1915 ◽  
Author(s):  
Ramin Alemzadeh ◽  
Gina Langley ◽  
Lori Upchurch ◽  
Pam Smith ◽  
Alfred E. Slonim
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Body Fat ◽  
Therapeutic Potential ◽  
Controlled Trial ◽  
Insulin Response ◽  
Tolerance Test ◽  
Fat Free Mass ◽  
Zucker Rats ◽  
Significant Difference

Hyperinsulinemia, insulin resistance, and increased adipose tissue are hallmarks of the obesity state in both humans and experimental animals. The role of hyperinsulinemia as a possible preceding event in the development of obesity has been proposed. We previously demonstrated that administration of diazoxide (DZ), an inhibitor of insulin secretion, to obese hyperinsulinemic Zucker rats resulted in less weight gain, enhanced insulin sensitivity, and improved glucose tolerance. Assuming that hyperinsulinemia plays a major role in the development of human obesity, then its reversal should have therapeutic potential. To test this hypothesis, we conducted a randomized placebo-controlled trial in 24 hyperinsulinemic adults [body mass index (BMI) > 30 kg/m2]. All subjects were placed on a low-calorie (1260 for females and 1570 for males) Optifast (Sandoz, Minneapolis, MN) diet. After an initial 1-week lead-in period, 12 subjects (mean ± se for age and BMI, 31 ± 1 and 40 ± 2, respectively) received DZ (2 mg/kg BW·day; maximum, 200 mg/day, divided into 3 doses) for 8 weeks; and 12 subjects (mean± se for age and BMI, 28 ± 1 and 43 ± 1, respectively) received placebo. Compared with the placebo group, DZ subjects had greater weight loss (9.5 ± 0.69% vs. 4.6 ± 0.61%, P < 0.001), greater decrease in body fat (P < 0.01), greater increase in fat-free mass to body fat ratio (P < 0.01), and greater attenuation of acute insulin response to glucose (P < 0.01). However, there was no significant difference in insulin sensitivity and glucose effectiveness, as determined by the insulin-modified iv glucose tolerance test (Bergman’s minimal model) and no significant difference in glycohemoglobin values. Conclusion: 8 weeks treatment with DZ had a significant antiobesity effect in hyperinsulinemic obese adults without inducing hyperglycemia.

scholarly journals Glucose tolerance and insulin sensitivity in malnourished children

1972 ◽  
Vol 27 (3) ◽  
pp. 585-592 ◽  
Author(s):  
G. A. O. Alleyne ◽  
P. M. Trust ◽  
H. Flores ◽  
H. Robinson
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Fasting Blood Glucose ◽  
Insulin Response ◽  
Malnourished Child ◽  
Normal Children ◽  
Intravenous Glucose ◽  
Malnourished Children ◽  
Isocaloric Diets ◽  
Blood Glucose Concentrations

1. In malnourished, compared with recovered children, fasting blood glucose concentrations were low and there was impaired peripheral glycolysis as shown by a failure of blood lactate to rise after glucose was injected intravenously.2. Homogenates of muscle biopsies from malnourished and recovered children produced equal amounts of lactate when incubated anaerobically with various substrates, but when compared with homogenates of biopsies from normal children the pattern suggested an impairment of glycolysis.3. The rate of glucose disappearance after intravenous glucose was slow in the malnourished child and there was possibly diminished sensitivity to exogenous insulin.4. Isocaloric diets relatively high or low in fat were fed to children who had recovered from malnutrition. Glucose tolerance, insulin sensitivity, fasting plasma insulin and insulin response to intravenous glucose were all the same in children on either diet.

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.

Effect of acute exercise and prolonged training on insulin response to intravenous glucose in vivo in rat

1983 ◽  
Vol 55 (6) ◽  
pp. 1660-1664 ◽  
Author(s):  
D. E. James ◽  
K. M. Burleigh ◽  
E. W. Kraegen ◽  
D. J. Chisholm
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Physical Training ◽  
Acute Exercise ◽  
Insulin Response ◽  
Intravenous Glucose ◽  
Intensive Training ◽  
Single Bout ◽  
Intravenous Glucose Tolerance Tests

Physical training causes hypoinsulinemia and enhanced insulin sensitivity. Insulin sensitivity is also enhanced by a single bout of exercise. However, changes in beta-cell responsiveness with acute exercise are ill defined. To clarify these relationships intravenous glucose tolerance tests were performed in 1) physically trained rats (3 different levels), 48 h after the last bout of exercise; 2) untrained rats, 0.5, 4, and 24 h after a single bout of exercise; or 3) sedentary control rats. The total area under the glucose-stimulated insulin response curve (GSIR) was negatively correlated with total distance run during training (r = -0.45, P less than 0.05), whereas glucose tolerance was improved (P less than 0.005 vs. controls) with intensive training. GSIR was suppressed by 38% (P less than 0.01 vs. controls) 0.5 h after a single bout of exercise. This effect persisted for 4 h but was not present after 24 h. These results indicate that a single bout of exercise induces suppression of GSIR which lasts less than 24 h. In contrast, physical training induces prolonged suppression (for at least 48 h) of GSIR, proportional to the intensity of training, and improved glucose tolerance.

scholarly journals Transgenerational metabolic outcomes associated with uteroplacental insufficiency

2013 ◽  
Vol 217 (1) ◽  
pp. 105-118 ◽  
Author(s):  
Melanie Tran ◽  
Linda A Gallo ◽  
Andrew J Jefferies ◽  
Karen M Moritz ◽  
Mary E Wlodek
Keyword(s):  
Insulin Secretion ◽  
Birth Weight ◽  
Glucose Tolerance ◽  
Cell Mass ◽  
Insulin Response ◽  
Whole Body ◽  
Model Assessment ◽  
Β Cell ◽  
Pancreatic Morphology ◽  
First Phase Insulin Response

Intrauterine growth restriction increases adult metabolic disease risk with evidence to suggest that suboptimal conditions in utero can have transgenerational effects. We determined whether impaired glucose tolerance, reduced insulin secretion, and pancreatic deficits are evident in second-generation (F2) male and female offspring from growth-restricted mothers, in a rat model of uteroplacental insufficiency. Late gestation uteroplacental insufficiency was induced by bilateral uterine vessel ligation (restricted) or sham surgery (control) in Wistar-Kyoto rats. First-generation (F1) control and restricted females were mated with normal males and F2 offspring studied at postnatal day 35 and at 6 and 12 months. F2 glucose tolerance, insulin secretion, and sensitivity were assessed at 6 and 12 months and pancreatic morphology was quantified at all study ages. At 6 months, F2 restricted male offspring exhibited blunted first-phase insulin response (−35%), which was associated with reduced pancreatic β-cell mass (−29%). By contrast, F2 restricted females had increased β-cell mass despite reduced first-phase insulin response (−38%). This was not associated with any changes in plasma estradiol concentrations. Regardless of maternal birth weight, F2 control and restricted males had reduced homeostatic model assessment of insulin resistance and elevated plasma triglyceride concentrations at 6 months and reduced whole-body insulin sensitivity at 6 and 12 months compared with females. We report that low maternal birth weight is associated with reduced first-phase insulin response and gender-specific differences in pancreatic morphology in the F2. Further studies will define the mode(s) of disease transmission, including direct insults to developing gametes, adverse maternal responses to pregnancy, or inherited mechanisms.

scholarly journals Determining insulin sensitivity from glucose tolerance tests in Iberian and landrace pigs

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11014
Author(s):  
José Miguel Rodríguez-López ◽  
Manuel Lachica ◽  
Lucrecia González-Valero ◽  
Ignacio Fernández-Fígares
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Early Stage ◽  
Insulin Response ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Glucose Infusion ◽  
Sensitivity Index ◽  
Post Infusion

As insulin sensitivity may help to explain divergences in growth and body composition between native and modern breeds, metabolic responses to glucose infusion were measured using an intra-arterial glucose tolerance test (IAGTT). Iberian (n = 4) and Landrace (n = 5) barrows (47.0 ± 1.2 kg body weight (BW)), fitted with a permanent carotid artery catheter were injected with glucose (500 mg/kg BW) and blood samples collected at -10, 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120 and 180 min following glucose infusion. Plasma samples were analysed for insulin, glucose, lactate, triglycerides, cholesterol, creatinine, albumin and urea. Insulin sensitivity indices were calculated and analysed. Mean plasma glucose, creatinine and cholesterol concentrations were lower (P < 0.01) in Iberian (14, 68 and 22%, respectively) than in Landrace pigs during the IAGTT. However, mean plasma insulin, lactate, triglycerides and urea concentrations were greater (P < 0.001) in Iberian (50, 35, 18 and 23%, respectively) than in Landrace pigs. Iberian pigs had larger area under the curve (AUC) of insulin (P < 0.05) or tended to a greater AUC of lactate (P < 0.10), and a smaller (P < 0.05) AUC for glucose 0-60 min compared with Landrace pigs. Indices for estimating insulin sensitivity in fasting conditions indicated improved β-cell function in Iberian compared with Landrace pigs, but no difference (P > 0.10) in calculated insulin sensitivity index was found after IAGTT between breeds. A time response (P < 0.05) was obtained for insulin, glucose and lactate so that maximum concentration was achieved at 10 and 15 min post-infusion for insulin (Iberian and Landrace pigs, respectively), immediately post-infusion for glucose, and 20 min post-infusion for lactate, decreasing thereafter until basal levels. There was no time effect for the rest of metabolites evaluated. In conclusion, growing Iberian pigs challenged with an IAGTT showed changes in biochemical parameters and insulin response that may indicate an early stage of insulin resistance.

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