INCREASED INSULIN SENSITIVITY AND CELLULAR INSULIN BINDING IN OBESE DIABETICS FOLLOWING TREATMENT WITH GLIBENCLAMIDE

1979 ◽  
Vol 90 (3) ◽  
pp. 451-462 ◽  
Author(s):  
Henning Beck-Nielsen ◽  
Oluf Pedersen ◽  
Hans Otto Lindskov
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Binding Affinity ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
Significant Alteration ◽  
Diabetic State ◽  
Before And After ◽  
Secretory Pattern

ABSTRACT The aim of the present study was to examine the effect of glibenclamide on the insulin receptors, the insulin sensitivity and the insulin secretion in obese non-ketotic diabetics. Two groups of 9 obese diabetics were studied before and after 10 days' treatment with a 1200 Kcal's diet and a 1200 kcal's diet + 10 mg/day of glibenclamide, respectively. In the group treated with diet alone we found no significant alteration of the insulin secretion pattern (P > 0.1). However, the insulin sensitivity increased 37 % (P < 0.01). Furthermore, the insulin binding to monocytes increased (P < 0.01) due to a 36% rise of the binding affinity. In the group treated with glibenclamide and diet the insulin secretory pattern was unchanged, too (P > 0.1). The insulin sensitivity, however, increased 83% (P < 0.01). Moreover, the insulin binding was raised (P < 0.01) as a result of a 80 % rise of the number of insulin receptors. In 4 patients who were treated with diet (1200 kcal/day) plus glibenclamide and in 5 patients who were treated with diet alone (1200 kcal/day) the insulin binding to monocytes was studied during treatment for 1 year. After 1 year we found a significantly (P < 0.05) higher cellular insulin binding in the glibenclamide treated patients compared to the patients who got diet alone. We conclude that 1) the augmentation of the insulin sensitivity is of great importance for the normalization of the diabetic state in obese, 2) the increase in insulin binding may be of importance for the increase in insulin sensitivity, 3) glibenclamide appears to enhance the insulin sensitivity through an increase in the number of insulin receptors.

Desensitization of beta-adrenergic receptors in adipocytes causes increased insulin sensitivity of glucose transport

1996 ◽  
Vol 271 (2) ◽  
pp. E271-E276 ◽  
Author(s):  
A. Green ◽  
R. M. Carroll ◽  
S. B. Dobias
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Transport ◽  
Adrenergic Receptors ◽  
Plasma Membranes ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
High Dose ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic ◽  
Adipocyte Plasma Membranes

To determine the effect of desensitization of adipocyte beta-adrenergic receptors on insulin sensitivity, rats were continuously infused with isoproterenol (50 or 100 micrograms.kg-1.h-1) for 3 days by osmotic minipumps. Epididymal adipocytes were isolated. The cells from treated animals were desensitized to isoproterenol, as determined by response of lipolysis (glycerol release). Binding of [125I]iodocyanopindolol was decreased by approximately 80% in adipocyte plasma membranes isolated from treated rats, indicating that beta-adrenergic receptors were downregulated. Cellular concentrations of Gn alpha and Gi alpha were not altered. Insulin sensitivity was determined by measuring the effect of insulin on glucose transport (2-deoxy-[3H]glucose uptake). Cells from the isoproterenol-infused rats were markedly more sensitive to insulin than those from control rats. This was evidenced by an approximately 50% increase in maximal glucose transport rate in cells from the high-dose isoproterenol-treated rats and by an approximately 40% decrease in the half-maximal effective concentration of insulin in both groups. 125I-labeled insulin binding to adipocytes was not altered by the isoproterenol infusions, indicating that desensitization of beta-adrenergic receptors results in tighter coupling between insulin receptors and stimulation of glucose transport.

scholarly journals Insulin Secretion and Insulin Sensitivity Before and After Surgical Treatment of Pheochromocytoma or Paraganglioma

2017 ◽  
Vol 102 (9) ◽  
pp. 3400-3405 ◽  
Author(s):  
Hisako Komada ◽  
Yushi Hirota ◽  
Anna So ◽  
Tomoaki Nakamura ◽  
Yoko Okuno ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Surgical Treatment ◽  
Insulin Sensitivity ◽  
Before And After

scholarly journals Influence of Tacrolimus on Glucose Metabolism before and after Renal Transplantation: A Prospective Study

2001 ◽  
Vol 12 (3) ◽  
pp. 583-588 ◽  
Author(s):  
ELLY M. VAN DUIJNHOVEN ◽  
JOHANNES M. M. BOOTS ◽  
MAARTEN H. L. CHRISTIAANS ◽  
BRUCE H. R. WOLFFENBUTTEL ◽  
JOHANNES P. VAN HOOFF
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
Prospective Longitudinal Study ◽  
C Peptide ◽  
Before And After ◽  
Prospective Longitudinal

Abstract. Most studies concerning the influence of tacrolimus on glucose metabolism have been performed either in animals or after organ transplantation. These clinical studies have largely been transversal with patients who were using steroids. Therefore, this prospective, longitudinal study investigated the influence of tacrolimus on glucose metabolism before and after transplantation. Eighteen Caucasian dialysis patients underwent an intravenous glucose tolerance test before and 5 d after the start of tacrolimus. Insulin sensitivity index (kG), insulin resistance (insulin/glucose ratio and homeostasis model assessment), and C-peptide and insulin secretion were calculated. Trough levels of tacrolimus were measured. After transplantation, the occurrence of posttransplantation diabetes mellitus (PTDM) was prospectively monitored. Statistical analysis was performed using the Wilcoxon signed ranks test and Spearman's rho for correlation. Before tacrolimus, kG was indeterminate in three patients. During tacrolimus, kG decreased in 16 of 18 patients, from a median of 1.74 mmol/L per min to 1.08 mmol/L per min (P < 0.0001). The correlation between C-peptide and insulin data was excellent. Insulin secretion decreased from 851.0 mU × min/L to 558.0 mU × min/L (P = 0.014), whereas insulin resistance did not change. Insulin sensitivity correlated negatively with tacrolimus trough level. After transplantation, three patients developed PTDM; before tacrolimus, two had an indeterminate and one a low normal kG. During tacrolimus administration, kG decreased in almost all patients as a result of a diminished insulin secretion response to a glucose load, whereas insulin resistance did not change. Patients with an abnormal or indeterminate kG seem to be at risk of developing PTDM while on tacrolimus.

Insulin secretion, adipocyte insulin binding and insulin sensitivity in thyrotoxicosis

1985 ◽  
Vol 109 (1) ◽  
pp. 96-103 ◽  
Author(s):  
Roy Taylor ◽  
Alan J. McCulloch ◽  
Stefan Zeuzem ◽  
Peter Gray ◽  
Frederick Clark ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Insulin Receptor ◽  
Insulin Binding ◽  
Immunoreactive Insulin ◽  
Oral Glucose ◽  
Maximum Displacement ◽  
Peripheral Tissues ◽  
Peptide Peak ◽  
Receptor Number

Abstract. The pattern of insulin secretion following an oral glucose load and the insulin receptor status and insulin sensitivity of adipocytes have been studied in patients with thyrotoxicosis and in matched controls. Thyrotoxic subjects showed normal basal and peak levels of serum immunoreactive insulin (peak, 69.0 ± 6.8 vs 54.3 ± 8.8 mU/l) and serum C-peptide (peak, 1.95 ± 0.13 vs 1.71 ±0.12 nmol/l for thyrotoxic and control subjects, respectively). Peak serum proinsulin was higher in the thyrotoxic group (64.8 ± 7.3 vs 39.0 ± 3.7 pmol/l; P < 0.01). Maximum specific insulin binding to adipocytes was decreased in the thyrotoxic group (1.80 ± 0.18 vs 2.62 ±0.27%; P< 0.025) and half-maximum displacement of tracer insulin was similar in the two groups, suggesting that reduced receptor number rather than reduced affinity accounted for the difference. However, adipocyte insulin sensitivity was normal as judged by half-maximal stimulation values of 13.9 ± 3.6 vs 11.4 ± 2.1 pmol/l, respectively for lipogenesis and 24.3 ± 2.2 vs 24.6 ± 3.6 pmol/l, respectively for glucose transport. Hence, thyroid hormone excess appears to affect adipocyte insulin receptor number directly, but change in receptor number is not associated with change in adipocyte insulin sensitivity in hyperthyroidism. The normal insulin secretion together with the failure to demonstrate abnormal insulin sensitivity of one of the major peripheral tissues suggests that disturbed hepatic rather than peripheral insulin responsiveness may be responsible for the glucose intolerance of hyperthyroidism.

scholarly journals Obesity is associated with increased basal and postprandial β-cell insulin secretion even in the absence of insulin resistance

2020 ◽  
Author(s):  
Ada Admin ◽  
Stephan van Vliet ◽  
Han-Chow E. Koh ◽  
Bruce W. Patterson ◽  
Mihoko Yoshino ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Production ◽  
Compensatory Response ◽  
Insulin Kinetics ◽  
Positron Emission ◽  
Glucose Ingestion ◽  
Before And After

We tested the hypothesis that obesity, independent of insulin resistance, is associated with increased insulin secretion. We compared insulin kinetics before and after glucose ingestion in lean healthy people and people with obesity who were matched on multi-organ insulin sensitivity (inhibition of adipose tissue lipolysis and glucose production and stimulation of muscle glucose uptake), assessed by using a two-stage hyperinsulinemic-euglycemic pancreatic clamp procedure in conjunction with glucose and palmitate tracer infusions and positron emission tomography. We also evaluated the effect of diet-induced weight loss on insulin secretion in people with obesity who did not improve insulin sensitivity despite marked (~20%) weight loss. Basal and postprandial insulin secretion rates were more than 50% greater in people with obesity than lean people even though insulin sensitivity was not different between groups. Weight loss in people with obesity decreased insulin secretion by 35% even though insulin sensitivity did not change. These results demonstrate that increased insulin secretion in people with obesity is associated with excess adiposity itself and is not simply a compensatory response to insulin resistance. These findings have important implications regarding the pathogenesis of diabetes, because hyperinsulinemia causes insulin resistance and insulin hypersecretion is an independent risk factor for developing diabetes.

scholarly journals Insulin secretion and insulin sensitivity in diabetic subgroups: studies in the prediabetic and diabetic state

Diabetologia ◽  
2000 ◽  
Vol 43 (12) ◽  
pp. 1476-1483 ◽  
Author(s):  
D. Tripathy ◽  
&#x000C5;.-L. Carlsson ◽  
M. Lehto ◽  
B. Isomaa ◽  
T. Tuomi ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Diabetic State

THE INSULIN RECEPTOR IN NORMAL AND OBESE PERSONS

1976 ◽  
Vol 83 (3) ◽  
pp. 565-575 ◽  
Author(s):  
Henning Beck-Nielsen ◽  
Oluf Pedersen ◽  
Jens Peder Bagger ◽  
Niels Schwartz Sørensen
Keyword(s):  
Plasma Insulin ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
Fat Cell ◽  
Ideal Weight ◽  
Comparable Group ◽  
Significant Difference ◽  
Before And After ◽  
Obese Subjects ◽  
Mononuclear Leucocytes

ABSTRACT Using [125I]insulin at 172 pmol/l (1 ng/ml) the binding of insulin to mononuclear leucocytes isolated from peripheral blood was studied. Our present study comprised 21 healthy subjects (22–33 years old, 90–110% of ideal weight) and a comparable group of 22 obese subjects (20–37 years old, minimum 150% of ideal weight). A significant difference in insulin binding was found between the two groups, the mean specific insulin binding fraction in normals being 1.92 ± 0.58 (s) × 10−2 and that for the obese 1.19 ± 0.41 (s) × 10−2 (P < 0.01). No correlation was found between body weight and the number of insulin receptors in the obese subjects. However, the number of insulin receptors was negatively correlated to fat cell size (P < 0.05). Insulin receptors in subjects were also negatively correlated to fasting plasma insulin (P < 0.05). Insulin receptors were studied in 11 obese subjects before and after 10 days of fasting. A significant increase in the number of insulin receptors was observed with a simultaneous decrease in plasma insulin to normal values. The results indicate that obesity complicated by hyperinsulinism is associated with a decrease in the number of insulin receptors compared with the normal. This finding may in part explain the decreased insulin sensitivity of the hyperinsulinaemic obese.

scholarly journals Obesity is associated with increased basal and postprandial β-cell insulin secretion even in the absence of insulin resistance

2020 ◽  
Author(s):  
Ada Admin ◽  
Stephan van Vliet ◽  
Han-Chow E. Koh ◽  
Bruce W. Patterson ◽  
Mihoko Yoshino ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Production ◽  
Compensatory Response ◽  
Insulin Kinetics ◽  
Positron Emission ◽  
Glucose Ingestion ◽  
Before And After

We tested the hypothesis that obesity, independent of insulin resistance, is associated with increased insulin secretion. We compared insulin kinetics before and after glucose ingestion in lean healthy people and people with obesity who were matched on multi-organ insulin sensitivity (inhibition of adipose tissue lipolysis and glucose production and stimulation of muscle glucose uptake), assessed by using a two-stage hyperinsulinemic-euglycemic pancreatic clamp procedure in conjunction with glucose and palmitate tracer infusions and positron emission tomography. We also evaluated the effect of diet-induced weight loss on insulin secretion in people with obesity who did not improve insulin sensitivity despite marked (~20%) weight loss. Basal and postprandial insulin secretion rates were more than 50% greater in people with obesity than lean people even though insulin sensitivity was not different between groups. Weight loss in people with obesity decreased insulin secretion by 35% even though insulin sensitivity did not change. These results demonstrate that increased insulin secretion in people with obesity is associated with excess adiposity itself and is not simply a compensatory response to insulin resistance. These findings have important implications regarding the pathogenesis of diabetes, because hyperinsulinemia causes insulin resistance and insulin hypersecretion is an independent risk factor for developing diabetes.

scholarly journals Secretory function of adipose tissue

2016 ◽  
Vol 19 (2) ◽  
pp. 441-446 ◽  
Author(s):  
J. Kuryszko ◽  
P. Sławuta ◽  
G. Sapikowski
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Insulin Receptors ◽  
Endocrine Function ◽  
Endocrine Gland ◽  
Main Function ◽  
Secretory Function ◽  
Brown Adipose

Abstract There are two kinds of adipose tissue in mammals: white adipose tissue – WAT and brown adipose tissue – BAT. The main function of WAT is accumulation of triacylglycerols whereas the function of BAT is heat generation. At present, WAT is also considered to be an endocrine gland that produces bioactive adipokines, which take part in glucose and lipid metabolism. Considering its endocrine function, the adipose tissue is not a homogeneous gland but a group of a few glands which act differently. Studies on the secretory function of WAT began in 1994 after discovery of leptin known as the satiation hormone, which regulates body energy homeostasis and maintainence of body mass. Apart from leptin, the following belong to adipokines: adiponectin, resistin, apelin, visfatin and cytokines: TNF and IL 6. Adiponectin is a polypeptide hormone of antidiabetic, anti-inflammatory and anti-atherogenic activity. It plays a key role in carbohydrate and fat metabolism. Resistin exerts a counter effect compared to adiponectin and its physiological role is to maintain fasting glycaemia. Visfatin stimulates insulin secretion and increases insulin sensitivity and glucose uptake by muscle cells and adipocytes. Apelin probably increases the insulin sensitivity of tissues. TNF evokes insulin resistance by blocking insulin receptors and inhibits insulin secretion. Approximately 30% of circulating IL 6 comes from adipose tissue. It causes insulin resistance by decreasing the expression of insulin receptors, decreases adipogenesis and adiponectin and visfatin secretion, and stimulates hepatic gluconeogenesis. In 2004, Bays introduced the notion of adiposopathy, defined as dysfunction of the adipose tissue, whose main feature is insulin and leptin resistance as well as the production of inflammatory cytokines: TNF and IL 6 and monocyte chemoattractant protein. This means that excess of adipose tissue, especially visceral adipose tissue, leads to the development of a chronic subclinical inflammatory condition, which favours the development of insulin resistance and Type 2 diabetes. Obesity is a systemic illness caused by energy transformation homeostasis disorder which results in an increase in the amount of body fat mass. It effects approximately 40% of dogs and 20% of cats. Illnesses which accompany obesity result, to a great extent, from the secretive role of adipose tissue, which is still little known, which should be included when planning treatment of an obese animal.

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