Reduced GLP-1 and insulin responses and glucose intolerance after gastric glucose in GRP receptor-deleted mice

2000 ◽  
Vol 279 (5) ◽  
pp. E956-E962 ◽  
Author(s):  
Kristin Persson ◽  
Ronald L. Gingerich ◽  
Sonali Nayak ◽  
Keiji Wada ◽  
Etsuko Wada ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Insulin Response ◽  
Biologically Active ◽  
Simultaneous Increase ◽  
Glucose Challenge ◽  
Elisa Technique ◽  
Genetic Targeting ◽  
Grp Receptors ◽  
Insulin Responses ◽  
Grp Receptor

By applying a newly developed ELISA technique for determining biologically active intact glucagon-like peptide [GLP-1, GLP-1-(7–36)amide] in mouse, plasma baseline GLP-1 in normal NMRI mice was found to be normally distributed (4.5 ± 0.3 pmol/l; n = 72). In anesthetized mice, gastric glucose (50 or 150 mg) increased plasma GLP-1 levels two- to threefold ( P < 0.01). The simultaneous increase in plasma insulin correlated to the 10-min GLP-1 levels ( r = 0.36, P < 0.001; n = 12). C57BL/6J mice deleted of the gastrin-releasing peptide (GRP) receptor by genetic targeting had impaired glucose tolerance ( P = 0.030) and reduced early (10 min) insulin response ( P = 0.044) to gastric glucose compared with wild-type controls. Also, the GLP-1 response to gastric glucose was significantly lower in the GRP receptor-deleted mice than in the controls ( P = 0.045). In conclusion, this study has shown that 1) plasma levels of intact GLP-1 increase dose dependently on gastric glucose challenge in correlation with increased insulin levels in mice, and 2) intact GRP receptors are required for normal GLP-1 and insulin responses and glucose tolerance after gastric glucose in mice.

Endocrine pancreatic function in women with gestational diabetes

1986 ◽  
Vol 113 (3_Suppl) ◽  
pp. S19-S23 ◽  
Author(s):  
Claus Kühl ◽  
Peter J. Hornnes
Keyword(s):  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Pregnant Women ◽  
Insulin Response ◽  
Normal Glucose Tolerance ◽  
Oral Glucose ◽  
Insulin Degradation ◽  
Insulinogenic Index ◽  
Insulin Responses ◽  
In Pregnancy

Abstract. Glucose tolerance deteriorates in normal human pregnancy but 99% of all pregnant women retain normal glucose tolerance whereas the remaining 1% develop abnormal glucose tolerance and are designated gestational diabetics. The possibility that glucose tolerance deteriorates in pregnancy because of diabetes-like changes in the secretory function of the endocrine pancreas has been investigated in gestational diabetics and healthy controls. Even though the insulin responses to oral glucose and mixed meals are equally large in gestational diabetics and normal pregnant women, the insulin responses of the gestational diabetics differ in two pertinent ways from those of the normals. First, a delayed insulin response is frequently seen, and second, the insulin response per unit of glycaemic stimulus (the 'insulinogenic index') is normally significantly lower than that of the normal pregnant women. Diabetes-like changes in the secretion of glucagon are not seen in neither group. Insulin degradation is unaffected by pregnancy and the proinsulin share of the total plasma insulin immunoreactivity does not increase in pregnancy. It is therefore likely that the main reason for the diabetogenicity of pregnancy is insulin resistance. Most pregnant women are able to increase their insulin secretion and thus overcome the resistance. Some pregnant women do, however, seem to have a more limited insulin secretory capacity which eventually may lead to the development of gestational diabetes.

Further support for heterogeneity of insulin response and insulin sensitivity in non-obese subjects with glucose intolerance

1983 ◽  
Vol 102 (3) ◽  
pp. 410-415 ◽  
Author(s):  
K. P. Ratzmann ◽  
S. Witt ◽  
B. Schulz
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Insulin Response ◽  
Normal Glucose Tolerance ◽  
Oral Glucose ◽  
Insulin Deficiency ◽  
Normal Glucose ◽  
Obese Subjects ◽  
Insulin Responses

Abstract. The relationship of insulin secretion and insulin sensitivity was studied in 67 age- and body weight-matched non-obese subjects, classified as having a normal glucose tolerance or glucose intolerance (50 g oral glucose load). Insulin response was studied by means of a 2 h glucose infusion. For the determination of insulin sensitivity a 1 h priming dose-constant insulin infusion technique was used. The per cent decrease of plasma glucose level at comparable steady-state insulin levels served as a measure of body sensitivity to exogenous insulin. In patients with glucose intolerance the early (ΔIRI area 0–5 min) and late (ΔIRI area 30–120 min) insulin responses to iv glucose were significantly reduced in comparison to controls. Controls and subjects with glucose intolerance showed considerable heterogeneity of insulin responses. Patients with glucose intolerance and relative insulin deficiency were not less responsive to insulin than subjects with normal glucose tolerance. There was, however, a wide variation of insulin sensitivity within the two groups. There was a weak significant inverse correlation between insulin response to glucose and insulin sensitivity for the two groups combined and for controls and subjects with glucose intolerance separately. The results demonstrate that the majority of non-obese patients with glucose intolerance and relative insulin deficiency does not exhibit a reduced responsiveness to insulin and therefore hypoinsulinaemia but not insulin resistance is the primary defect for an abnormal glucose tolerance in these group of subjects.

GLUCOSE TOLERANCE AND INSULIN SECRETION IN HYPERTHYROIDISM

1977 ◽  
Vol 84 (3) ◽  
pp. 576-587 ◽  
Author(s):  
O. Ortved Andersen ◽  
Th. Friis ◽  
B. Ottesen
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Cell Mass ◽  
Insulin Response ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Glucose Response ◽  
Intravenous Glucose ◽  
Insulin Responses

ABSTRACT To evaluate the glucose tolerance and insulin secretion in hyperthyroidism patients were examined in the toxic state and after they had been made euthyroid. Fasting values: In 42 untreated patients the glucose- and insulin concentrations in serum were significantly elevated. In 24 treated patients the glucose concentrations became normal, while the insulin concentrations remained elevated. Oral-glucose-tolerance test: In 20 untreated patients the glucose- and insulin responses were significantly increased. In 8 treated patients the glucose response became normal, while the insulin response remained unchanged. Intravenous-glucose-tolerance test: In 28 untreated patients the K-values were significantly decreased and the insulin response increased. In 23 treated patients the K-values rose significantly, but the insulin response remained unchanged. Intravenous-tolbutamide test: In 41 untreated patients the glucose concentration decreased significantly compared with the controls, and the insulin responses were significantly increased. In 23 treated patients the glucose concentrations decreased even more, while the insulin response remained unchanged. The results indicate enhanced sensitivity or an increase in the mass of β-cells in hyperthyroidism. The glucose tolerance tests point to an increased peripheral insulin resistance. The normalized glucose tolerance and still enhanced insulin secretion during treatment support the assumption, that hyperthyroidism causes an increase in the β-cell mass.

scholarly journals The effect of systemic and ovarian infusion of glucose, galactose and fructose on ovarian function in sheep

Reproduction ◽  
2010 ◽  
Vol 140 (5) ◽  
pp. 721-732 ◽  
Author(s):  
B K Campbell ◽  
N R Kendall ◽  
V Onions ◽  
R J Scaramuzzi
Keyword(s):  
Low Dose ◽  
Ovarian Function ◽  
Ovarian Follicle ◽  
Insulin Response ◽  
Acute Effect ◽  
Arterial Infusion ◽  
Fourfold Increase ◽  
Glucose Challenge ◽  
Insulin Responses

Glucose is a critical metabolic fuel in most mammals although many foodstuffs also contain high levels of the monosaccharides, galactose and fructose. The aims of this work were to determine the insulin response to challenges of these sugars (experiment 1) and to examine the effect of systemic (experiment 2) and direct ovarian (experiment 3) infusion of these monosaccharides on ovarian function in ewes with autotransplanted ovaries. In experiment 1, both fructose (fourfold increase peaking in 2 h) and galactose (twofold increase; 30 min) elicited markedly different (P<0.001) insulin responses than glucose (sevenfold increase; 20 min) although the total amount released following fructose and glucose challenge was similar. In experiment 2, low-dose systemic fructose infusion had no acute effect on insulin but did depress FSH (P<0.05), and following the end of fructose infusion, a transient increase in FSH and insulin was observed (P<0.05), which was associated with an increase (P<0.05) in ovarian oestradiol and androstenedione secretion. Systemic infusion of neither glucose nor galactose had a significant effect on ovarian steroidogenesis although glucose acutely suppressed insulin levels. In contrast, ovarian arterial infusion of fructose and glucose had no effect on ovarian function whereas galactose suppressed ovarian follicle number and steroid secretion (P<0.05). In conclusion, this work indicates that fructose and galactose can influence ovarian functionin vivoin sheep and that different mechanisms are involved. Thus, fructose exerts stimulatory effects through indirect modulation of peripheral insulin and/or gonadotrophin levels whereas galactose exerts primarily suppressive effects by direct actions on the ovary.

Calcitonin modulation of insulin and glucagon secretion in man

1982 ◽  
Vol 242 (3) ◽  
pp. E206-E213 ◽  
Author(s):  
D. Giugliano ◽  
N. Passariello ◽  
S. Sgambato ◽  
R. Torella ◽  
F. D'Onofrio
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Insulin Response ◽  
Glucagon Secretion ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Acute Insulin Response ◽  
Insulin Responses ◽  
Effect Of Glucose

These studies were undertaken to evaluate the effect of different doses of calcitonin on insulin and glucagon responses to intravenous glucase loads and to assess the mechanism/s by which calcitonin inhibits insulin secretion in man. In our studies, even the infusion of the 1-U dose of calcitonin was found to inhibit by 45% the acute insulin response to a glucose (20 g) pulse. This effect was associated with a significant decrease in glucose disappearance rates. These negative effects of calcitonin on both insulin secretion and glucose tolerance were dose-related. The inhibition of the acute insulin response to glucose was 65% and up to 90% with the infusion of the 4- and 8-U doses, respectively. The suppressive effect of glucose on glucagon secretion was significantly reduced by calcitonin. The inhibitory effect of calcitonin on insulin responses to glucose (5 g) and glucose tolerance was reversed by both theophylline and calcium. By contrast, infusion of lysine acetylsalicylate to block the synthesis of endogenous prostaglandins did not diminish the inhibitory effect of calcitonin on insulin secretion. These results demonstrate that a) calcitonin inhibits glucose-induced insulin responses and deteriorates glucose tolerance in normal humans in a dose-dependent manner; b) calcitonin reduces the suppressive effect of glucose on glucagon secretion in a dose-related fashion; and c) both theophylline and calcium reverse the inhibitory effect of calcitonin on insulin secretion. It is hypothesized that calcitonin effects on insulin and glucagon release are mediated via a change in calcium redistribution in the islet cells.

Insulin responses during glucose tolerance tests in steers with increasing Wagyu genetic influence

1998 ◽  
Vol 78 (2) ◽  
pp. 233-235 ◽  
Author(s):  
P. S. Mir ◽  
G. J. Mears ◽  
C. M. Ross ◽  
S. D. Husar ◽  
W. M. Robertson ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Insulin Response ◽  
Genetic Influence ◽  
Marbling Score ◽  
Intravenous Glucose ◽  
Post Infusion ◽  
Glucose Tolerance Tests ◽  
Intravenous Glucose Tolerance Tests ◽  
Insulin Responses

Intravenous glucose tolerance tests (IVGTT) were conducted in 18 steers with 0, 50 and 75% Wagyu genetic influence. Glucose clearances were similar for all steers. Plasma insulin concentrations (basal, 5 and 10 min post-infusion) were higher (P < 0.05) in 0% Wagyu steers (2.57, 7.36, 9.68 ng mL−1) relative to 50% Wagyu (1.17, 2.59, 5.34 ng mL−1) or 75% Wagyu (0.99, 2.78, 5.00 ng mL−1). A correlation coefficient of 0.71 (P = 0.005; n = 15) between marbling score of carcasses and plasma glucose concentration 90 min after glucose infusion suggests, possible associations among the propensity of cattle with Wagyu genetic influence to marble, mechanisms of glucose utilization and nature of the insulin response to circulating glucose. Key words: Plasma glucose, insulin, marbling, Wagyu

Plasma insulin response among Nauruans. Prediction of deterioration in glucose tolerance over 6 yr

Diabetes ◽  
1987 ◽  
Vol 36 (2) ◽  
pp. 179-186 ◽  
Author(s):  
R. A. Sicree ◽  
P. Z. Zimmet ◽  
H. O. King ◽  
J. S. Coventry
Keyword(s):  
Glucose Tolerance ◽  
Plasma Insulin ◽  
Insulin Response ◽  
Plasma Insulin Response

scholarly journals Metabolomics analysis reveals altered metabolites in lean compared with obese adolescents and additional metabolic shifts associated with hyperinsulinaemia and insulin resistance in obese adolescents: a cross-sectional study

Metabolomics ◽  
2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Elisabeth Müllner ◽  
Hanna E. Röhnisch ◽  
Claudia von Brömssen ◽  
Ali A. Moazzami
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Glucose Tolerance ◽  
Insulin Response ◽  
Oral Glucose ◽  
Response Level ◽  
Metabolic Alterations ◽  
Obese Adolescents ◽  
Branched Chain ◽  
Metabolomics Analysis

Abstract Introduction Hyperinsulinaemia and insulin resistance (IR) are strongly associated with obesity and are forerunners of type 2 diabetes. Little is known about metabolic alterations separately associated with obesity, hyperinsulinaemia/IR and impaired glucose tolerance (IGT) in adolescents. Objectives To identify metabolic alterations associated with obesity, hyperinsulinaemia/IR and hyperinsulinaemia/IR combined with IGT in obese adolescents. Methods 81 adolescents were stratified into four groups based on body mass index (lean vs. obese), insulin responses (normal insulin (NI) vs. high insulin (HI)) and glucose responses (normal glucose tolerance (NGT) vs. IGT) after an oral glucose tolerance test (OGTT). The groups comprised: (1) healthy lean with NI and NGT, (2) obese with NI and NGT, (3) obese with HI and NGT, and (4) obese with HI and IGT. Targeted nuclear magnetic resonance-based metabolomics analysis was performed on fasting and seven post-OGTT plasma samples, followed by univariate and multivariate statistical analyses. Results Two groups of metabolites were identified: (1) Metabolites associated with insulin response level: adolescents with HI (groups 3–4) had higher concentrations of branched-chain amino acids and tyrosine, and lower concentrations of serine, glycine, myo-inositol and dimethylsulfone, than adolescents with NI (groups 1–2). (2) Metabolites associated with obesity status: obese adolescents (groups 2–4) had higher concentrations of acetylcarnitine, alanine, pyruvate and glutamate, and lower concentrations of acetate, than lean adolescents (group 1). Conclusions Obesity is associated with shifts in fat and energy metabolism. Hyperinsulinaemia/IR in obese adolescents is also associated with increased branched-chain and aromatic amino acids.

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