The effect of antipsychotic drugs on insulin sensitivity and insulin secretion

The ability to predict prediabetes, which affects ∼90 million adults in the US and ∼400 million adults worldwide, would be valuable to public health. Acylcarnitines, fatty acid metabolites, have been associated with type 2 diabetes risk in cross-sectional studies of mostly Caucasian subjects, but prospective studies on their link to prediabetes in diverse populations are lacking. Here, we determined the association of plasma acylcarnitines with incident prediabetes in African Americans and European Americans enrolled in a prospective study. We analyzed 45 acylcarnitines in baseline plasma samples from 70 adults (35 African-American, 35 European-American) with incident prediabetes (progressors) and 70 matched controls (non-progressors) during 5.5-year (mean 2.6 years) follow-up in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. Incident prediabetes (impaired fasting glucose/impaired glucose tolerance) was confirmed with OGTT. We measured acylcarnitines using tandem mass spectrometry, insulin sensitivity by hyperinsulinemic euglycemic clamp, and insulin secretion using intravenous glucose tolerance test. The results showed that progressors and non-progressors during POP-ABC study follow-up were concordant for 36 acylcarnitines and discordant for nine others. In logistic regression models, beta-hydroxy butyryl carnitine (C4-OH), 3-hydroxy-isovaleryl carnitine/malonyl carnitine (C5-OH/C3-DC), and octenoyl carnitine (C8:1) were the only significant predictors of incident prediabetes. The combined cut-off plasma levels of <0.03 micromol/L for C4-OH, <0.03 micromol/L for C5-OH/C3-DC, and >0.25 micromol/L for C8:1 acylcarnitines predicted incident prediabetes with 81.9% sensitivity and 65.2% specificity. Thus, circulating levels of one medium-chain and two short-chain acylcarnitines may be sensitive biomarkers for the risk of incident prediabetes among initially normoglycemic individuals with parental history of type 2 diabetes.

Download Full-text

Maternal diabetes alters birth weight in glucokinase-deficient (MODY2) kindred but has no influence on adult weight, height, insulin secretion or insulin sensitivity

Diabetologia ◽

10.1007/s001250051490 ◽

2000 ◽

Vol 43 (8) ◽

pp. 1060-1063 ◽

Cited By ~ 45

Author(s):

G. Velho ◽

A. T. Hattersley ◽

P. Froguel

Keyword(s):

Insulin Secretion ◽

Birth Weight ◽

Insulin Sensitivity ◽

Maternal Diabetes ◽

Adult Weight

Download Full-text

Diurnal variations in insulin secretion and insulin sensitivity in aged subjects

Acta Diabetologica Latina ◽

10.1007/bf02580997 ◽

1980 ◽

Vol 17 (2) ◽

pp. 153-160 ◽

Cited By ~ 6

Author(s):

Elisabetta Pisu ◽

Antonio Diana ◽

Alessandra Lombardi ◽

Maurizio Cassader ◽

Gianfranco Pagano

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Diurnal Variations ◽

Aged Subjects

Download Full-text

Insulin secretion, glucose production, and insulin sensitivity in underweight and normal-weight volunteers, and in underweight and normal-weight cancer patients: A Clinical Research Center Study

Metabolism ◽

10.1016/s0026-0495(97)90291-2 ◽

1997 ◽

Vol 46 (2) ◽

pp. 140-145 ◽

Cited By ~ 24

Author(s):

John A. Tayek ◽

Savita Manglik ◽

Elliot Abemayor

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Clinical Research ◽

Cancer Patients ◽

Glucose Production ◽

Normal Weight ◽

Research Center ◽

Clinical Research Center ◽

Center Study

Download Full-text

PWD/PhJ and WSB/EiJ Mice Are Resistant to Diet-Induced Obesity But Have Abnormal Insulin Secretion

Endocrinology ◽

10.1210/en.2011-0060 ◽

2011 ◽

Vol 152 (8) ◽

pp. 3005-3017 ◽

Cited By ~ 17

Author(s):

Katie T. Y. Lee ◽

Subashini Karunakaran ◽

Maggie M. Ho ◽

Susanne M. Clee

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Large Scale ◽

Mouse Strains ◽

Second Phase ◽

Fasting Insulin ◽

High Fat ◽

Diet Induced Obesity ◽

Obesity And Diabetes

Recently, novel inbred mouse strains that are genetically distinct from the commonly used models have been developed from wild-caught mice. These wild-derived inbred strains have been included in many of the large-scale genomic projects, but their potential as models of altered obesity and diabetes susceptibility has not been assessed. We examined obesity and diabetes-related traits in response to high-fat feeding in two of these strains, PWD/PhJ (PWD) and WSB/EiJ (WSB), in comparison with C57BL/6J (B6). Young PWD mice displayed high fasting insulin levels, although they had normal insulin sensitivity. PWD mice subsequently developed a much milder and delayed-onset obesity compared with B6 mice but became as insulin resistant. PWD mice had a robust first-phase and increased second-phase glucose-stimulated insulin secretion in vivo, rendering them more glucose tolerant. WSB mice were remarkably resistant to diet-induced obesity and maintained very low fasting insulin throughout the study. WSB mice exhibited more rapid glucose clearance in response to an insulin challenge compared with B6 mice, consistent with their low percent body fat. Interestingly, in the absence of a measurable in vivo insulin secretion, glucose tolerance of WSB mice was better than B6 mice, likely due to their enhanced insulin sensitivity. Thus PWD and WSB are two obesity-resistant strains with unique insulin secretion phenotypes. PWD mice are an interesting model that dissociates hyperinsulinemia from obesity and insulin resistance, whereas WSB mice are a model of extraordinary resistance to a high-fat diet.

Download Full-text

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.

Download Full-text