Antecedent protein restriction exacerbates development  of impaired insulin action after high-fat feeding

The study investigated whether a persistent impairment of insulin secretion resulting from mild protein restriction predisposes to loss of glucoregulatory control and impaired insulin action after the subsequent imposition of the diabetogenic challenge of high-fat feeding. Offspring of dams provided with either control (20% protein) diet (C) or an isocaloric restricted (8%) protein diet (PR) were weaned onto the maintenance diet with which their mothers had been provided. At 20 wk of age, protein restriction enhanced glucose tolerance despite impaired insulin secretion and an augmented and sensitized lipolytic response to norepinephrine in adipocytes. C and PR rats were then transferred to a high-fat diet (HF, 19% protein, 22% lipid, 34% carbohydrate) and sampled after 8 wk. These groups are termed C-HF and PR-HF. Glucose tolerance was impaired in PR-HF, but not C-HF, rats. Insulin-stimulated glucose disposal rates were significantly lower (by 30%; P < 0.01) in the PR-HF group than in the C-HF group, and a specific impairment of antilipolytic response of insulin was unmasked in adipocytes from PR-HF, but not C-HF, rats. The study demonstrates that antecedent protein restriction accelerates and augments the development of impaired glucoregulation and insulin resistance after high-fat feeding.

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Vagotomy Reduces Insulin Clearance in Obese Mice Programmed by Low-Protein Diet in the Adolescence

Neural Plasticity ◽

10.1155/2017/9652978 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Camila Lubaczeuski ◽

Luciana Mateus Gonçalves ◽

Jean Franciesco Vettorazzi ◽

Mirian Ayumi Kurauti ◽

Junia Carolina Santos-Silva ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

High Fat Diet ◽

Insulin Clearance ◽

Protein Diet ◽

Low Protein Diet ◽

High Fat ◽

Insulin Degrading Enzyme ◽

Low Protein

The aim of this study was to investigate the effect of subdiaphragmatic vagotomy on insulin sensitivity, secretion, and degradation in metabolic programmed mice, induced by a low-protein diet early in life, followed by exposure to a high-fat diet in adulthood. Weaned 30-day-old C57Bl/6 mice were submitted to a low-protein diet (6% protein). After 4 weeks, the mice were distributed into three groups: LP group, which continued receiving a low-protein diet; LP + HF group, which started to receive a high-fat diet; and LP + HFvag group, which underwent vagotomy and also was kept at a high-fat diet. Glucose-stimulated insulin secretion (GSIS) in isolated islets, ipGTT, ipITT, in vivo insulin clearance, and liver expression of the insulin-degrading enzyme (IDE) was accessed. Vagotomy improved glucose tolerance and reduced insulin secretion but did not alter adiposity and insulin sensitivity in the LP + HFvag, compared with the LP + HF group. Improvement in glucose tolerance was accompanied by increased insulinemia, probably due to a diminished insulin clearance, as judged by the lower C-peptide : insulin ratio, during the ipGTT. Finally, vagotomy also reduced liver IDE expression in this group. In conclusion, when submitted to vagotomy, the metabolic programmed mice showed improved glucose tolerance, associated with an increase of plasma insulin concentration as a result of insulin clearance reduction, a phenomenon probably due to diminished liver IDE expression.

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Leptin administration improves skeletal muscle insulin responsiveness in diet-induced insulin-resistant rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2001.280.1.e130 ◽

2001 ◽

Vol 280 (1) ◽

pp. E130-E142 ◽

Cited By ~ 44

Author(s):

Ben B. Yaspelkis ◽

James R. Davis ◽

Maziyar Saberi ◽

Toby L. Smith ◽

Reza Jazayeri ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Secretion ◽

Glucose Tolerance ◽

Glucose Uptake ◽

Whole Body ◽

Glucose Disposal ◽

High Fat ◽

Insulin Resistant ◽

Skeletal Muscle Glucose Uptake ◽

Uptake And Transport

In addition to suppressing appetite, leptin may also modulate insulin secretion and action. Leptin was administered here to insulin-resistant rats to determine its effects on secretagogue-stimulated insulin release, whole body glucose disposal, and insulin-stimulated skeletal muscle glucose uptake and transport. Male Wistar rats were fed either a normal (Con) or a high-fat (HF) diet for 3 or 6 mo. HF rats were then treated with either vehicle (HF), leptin (HF-Lep, 10 mg · kg−1 · day−1 sc), or food restriction (HF-FR) for 12–15 days. Glucose tolerance and skeletal muscle glucose uptake and transport were significantly impaired in HF compared with Con. Whole body glucose tolerance and rates of insulin-stimulated skeletal muscle glucose uptake and transport in HF-Lep were similar to those of Con and greater than those of HF and HF-FR. The insulin secretory response to either glucose or tolbutamide (a pancreatic β-cell secretagogue) was not significantly diminished in HF-Lep. Total and plasma membrane skeletal muscle GLUT-4 protein concentrations were similar in Con and HF-Lep and greater than those in HF and HF-FR. The findings suggest that chronic leptin administration reversed a high-fat diet-induced insulin-resistant state, without compromising insulin secretion.

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059. POOR GROWTH BEFORE BIRTH IMPAIRS INSULIN SECRETION - WHAT WE HAVE LEARNT ABOUT THE MECHANISMS FROM THE PLACENTALLY-RESTRICTED SHEEP

Reproduction Fertility and Development ◽

10.1071/srb09abs059 ◽

2009 ◽

Vol 21 (9) ◽

pp. 14

Author(s):

K. L. Gatford

Keyword(s):

Insulin Resistance ◽

Insulin Secretion ◽

Beta Cell ◽

Insulin Action ◽

Cell Function ◽

Cell Mass ◽

Beta Cell Mass ◽

Poor Growth ◽

Impaired Insulin ◽

Impaired Insulin Action

Diabetes occurs when insulin secretion fails to increase sufficiently to compensate for developing insulin resistance. This implies that the increased risk of diabetes in adults who were small at birth reflects impaired insulin secretion as well as their well-known insulin resistance. More recently, direct evidence has been obtained that adults and children who were growth-restricted before birth secrete less insulin than they should, given their level of insulin resistance. Our research group is using the placentally-restricted (PR) sheep to investigate the mechanisms underlying impaired insulin action (sensitivity and secretion) induced by poor growth before birth. Like the intra-uterine growth-restricted (IUGR) human, the PR sheep develops impaired insulin action by adulthood, but has enhanced insulin sensitivity in infancy, associated with neonatal catch-up growth1, 2. Impaired insulin action begins to develop in early postnatal life, where although basal insulin action is high due to enhanced insulin sensitivity, maximal glucose-stimulated insulin action is already impaired in males3. Our cellular and molecular studies have identified impaired beta-cell function rather than mass as the likely cause of impaired insulin secretion, and we have reported a novel molecular defect in the calcium channels involved in the insulin secretion pathway in the pancreas of these lambs3. Upregulation of IGF-II and insulin receptor are implicated as key molecular regulators of beta-cell mass in the PR lamb3. By adulthood, both basal and maximal insulin action are profoundly impaired in the male lamb who was growth-restricted at birth2. These studies suggest therapies to prevent diabetes in the individual who grew poorly before birth should target beta-cell function, possibly in addition to further increasing beta-cell mass, to improve insulin secretion capacity, and its ability to increase in response to development of insulin resistance. We are now using the PR sheep to test potential therapies, since the timing of pancreatic development and hence exposure to a growth-restricting environment, is similar to that of the human.

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Monitoring of Patient With Diabetes Mellitus

Jurnal Ilmiah Kedokteran Wijaya Kusuma ◽

10.30742/jikw.v3i2.23 ◽

2017 ◽

Vol 3 (2) ◽

pp. 55

Author(s):

Widodo Widodo

Keyword(s):

Diabetes Mellitus ◽

Insulin Secretion ◽

Blood Vessels ◽

Insulin Action ◽

Laboratory Tests ◽

Impaired Insulin Secretion ◽

Chronic Hyperglycemia ◽

Impaired Insulin ◽

Patients With Diabetes ◽

Impaired Insulin Action

Diabetes mellitus is a disease characterized by hyperglycemia, which is caused by impaired insulin secretion, impaired insulin action, or both. Chronic hyperglycemia will lead to dysfunction and damage to various organs, such as the eyes, kidneys, nerves, heart, and blood vessels. This paper discusses the monitoring of patients with diabetes mellitus according to the laboratory tests, to know when the results of therapy has reached the optimum point as well as the prevention of complications that can occur.

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Comparison of short-term diet and exercise on insulin action in individuals with abnormal glucose tolerance

Journal of Applied Physiology ◽

10.1152/jappl.1999.86.6.1930 ◽

1999 ◽

Vol 86 (6) ◽

pp. 1930-1935 ◽

Cited By ~ 49

Author(s):

Paul J. Arciero ◽

Matthew D. Vukovich ◽

John O. Holloszy ◽

Susan B. Racette ◽

Wendy M. Kohrt

Keyword(s):

Glucose Tolerance ◽

Insulin Action ◽

Fat Free Mass ◽

Glucose Disposal ◽

Abnormal Glucose Tolerance ◽

High Fat ◽

Short Term ◽

Arginine Infusion ◽

Hyperglycemic Clamp ◽

Calorie Diet

The effects of a 10-day low-calorie diet (LCD; n = 8) or exercise training (ET; n = 8) on insulin secretion and action were compared in obese men ( n = 9) and women ( n = 7), aged 53 ± 1 yr, with abnormal glucose tolerance by using a hyperglycemic clamp with superimposed arginine infusion and a high-fat drink. Body mass (LCD, 115 ± 5 vs. 110 ± 5 kg; ET, 111 ± 7 vs. 109 ± 7 kg; P < 0.01) and fasting plasma glucose (LCD, 115 ± 10 vs. 99 ± 4 mg/dl; ET, 112 ± 4 vs. 101 ± 5 mg/dl, P < 0.01) and insulin (LCD, 23.9 ± 5.6 vs. 15.2 ± 3.9 μU/ml; ET, 17.6 ± 1.9 vs. 13.9 ± 2.4 μU/ml; P < 0.05) decreased in both groups. There was a 40% reduction in plasma insulin during hyperglycemia (0–45 min) after LCD (peak: 118 ± 18 vs. 71 ± 14 μU/ml; P < 0.05) and ET (69 ± 14 vs. 41 ± 7 μU/ml; P < 0.05) and trends for reductions during arginine infusion and a high-fat drink. The 56% increase in glucose uptake after ET (4.95 ± 0.90 vs. 7.74 ± 0.82 mg ⋅ min−1 ⋅ kg fat-free mass−1; P < 0.01) was significantly ( P < 0.01) greater than the 19% increase (5.72 ± 1.12 vs. 6.80 ± 0.94 mg ⋅ min−1 ⋅ kg fat-free mass−1; P = not significant) that occurred after LCD. The marked increase in glucose disposal after ET, despite lower insulin levels, suggests that short-term exercise is more effective than diet in enhancing insulin action in individuals with abnormal glucose tolerance.

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