scholarly journals Incorporation of Unique, Diet-derived Fatty Acids into Hepatic Tissue Is Associated with Improved Glucose Homeostasis in Aged CD-1 Mice (OR24-02-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Allison Unger ◽  
Thomas Jetton ◽  
James Whitley ◽  
Jana Kraft
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Whole Body ◽  
Hepatic Tissue ◽  
Gas Liquid Chromatography ◽  
Mouse Population ◽  
Echium Oil ◽  
Dairy Fat ◽  
Fa Composition

Abstract Objectives We hypothesized that the chronic consumption of unique dietary FA derived from dairy fat and echium oil, respectively, would affect the FA composition and content of the hepatic tissue and correlate with parameters of glucose homeostasis in an aged, genetically heterogeneous mouse population. Our objectives were to i) measure glucose homeostasis, ii) determine the FA composition of hepatic tissue, and iii) correlate physiologic data and hepatic FA content by diet and sex. Methods From one month of age, CD-1 male and female mice (n = 10/diet/sex) were fed either a high-fat (40% total energy) control diet comprising of the FA composition of the typical U.S. American diet (CO), or an isoenergetic diet with 30% of CO fat replaced with dairy fat (BO) or echium oil (EO) for the study duration of 13 months. Every three months, whole-body glucose homeostasis was assessed (i.e., glucose tolerance and insulin tolerance tests (GTT and ITT, respectively)). At the end of the study, hepatic tissue was collected and analyzed for FA composition via gas-liquid chromatography. Results Hepatic content of stearidonic acid (SDA; 18:4 n-3) and γ-linolenic acid (18:3 n-6) was greatest in EO-fed mice (P < .0001). Mice fed a BO-diet had the greatest hepatic content of total odd- and branched-chain FA (OBCFA) and conjugated linoleic acids (P < .0001), as well as a greater hepatic content of 18:1 isomers compared to EO-fed mice (P < .001). In EO-fed females, hepatic content of SDA correlated with improved glucose tolerance, as determined by GTT area under the curve (r = −.94; P < 0.01), and in EO-fed males, hepatic content of SDA was positively associated with improved insulin sensitivity (r = .79; P < 0.05). In BO-fed males, hepatic content of total OCFA was negatively correlated with fasting plasma insulin levels (r = −.83; P < 0.05), and hepatic content of total iso BCFA was associated with improved insulin sensitivity (r = −.89; P < 0.05). Conclusions These findings demonstrate that habitual consumption of unique FA derived from dairy fat and echium oil influences hepatic FA composition and content and correlates with improvements in whole-body glucose homeostasis in an aged population. Furthermore, this study suggests that dietary fat quality may be part of an effective preventative strategy for metabolic diseases such as T2D in the elderly. Funding Sources Armin Grams Memorial Research Award, UVM Robert Larner, M.D. College of Medicine; USDA-NIFA Hatch Fund (accession number: 1006628).

scholarly journals Activin B regulates islet composition and islet mass but not whole body glucose homeostasis or insulin sensitivity

2012 ◽  
Vol 303 (5) ◽  
pp. E587-E596 ◽  
Author(s):  
Lara Bonomi ◽  
Melissa Brown ◽  
Nathan Ungerleider ◽  
Meghan Muse ◽  
Martin M. Matzuk ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Activin A ◽  
Whole Body ◽  
Null Mouse ◽  
Islet Function ◽  
Islet Mass ◽  
Glucose Stimulated Insulin Secretion

Based on the phenotype of the activin-like kinase-7 (ALK7)-null mouse, activins A and B have been proposed to play distinct roles in regulating pancreatic islet function and glucose homeostasis, with activin A acting to enhance islet function and insulin release while activin B antagonizes these actions. We therefore hypothesized that islets from activin B-null (BBKO) mice would have enhanced glucose-stimulated insulin secretion. In addition, we hypothesized that this enhanced islet function would translate into increased whole body glucose tolerance. We tested these hypotheses by analyzing glucose homeostasis, insulin secretion, and islet function in BBKO mice. No differences were observed in fasting glucose or insulin levels, glucose tolerance, or insulin sensitivity compared with weight-matched young or older males. Similarly, there were no significant differences in insulin secretion comparing islets from WT or BBKO males at either age. However, BBKO islets were more sensitive to activin A, myostatin (MSTN), and follistatin (FST) treatments, so that activin A and FST inhibited and MSTN enhanced glucose stimulated insulin secretion. While mean islet area and the distribution of islet areas were not different between the genotypes, islet mass, islet number, and the proportion of α-cells/islet were significantly reduced in BBKO islets. These results indicate that activin B does not antagonize activin A to influence whole body glucose homeostasis or β-cell function but does influence islet mass and proportion of α-cells/islet. Therefore, loss of activin B signaling alone does not account for the ALK7-null phenotype, but activin B may have important roles in modulating islet mass, islet number, and the cellular composition of islets.

scholarly journals Orexin receptors 1 and 2 in serotonergic neurons differentially regulate peripheral glucose metabolism in obesity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xing Xiao ◽  
Gagik Yeghiazaryan ◽  
Simon Hess ◽  
Paul Klemm ◽  
Anna Sieben ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Raphe Nucleus ◽  
Receptor Type ◽  
Serotonergic Neurons ◽  
Dynamic Regulation ◽  
Brown Adipose ◽  
Raphe Pallidus

AbstractThe wake-active orexin system plays a central role in the dynamic regulation of glucose homeostasis. Here we show orexin receptor type 1 and 2 are predominantly expressed in dorsal raphe nucleus-dorsal and -ventral, respectively. Serotonergic neurons in ventral median raphe nucleus and raphe pallidus selectively express orexin receptor type 1. Inactivation of orexin receptor type 1 in serotonin transporter-expressing cells of mice reduced insulin sensitivity in diet-induced obesity, mainly by decreasing glucose utilization in brown adipose tissue and skeletal muscle. Selective inactivation of orexin receptor type 2 improved glucose tolerance and insulin sensitivity in obese mice, mainly through a decrease in hepatic gluconeogenesis. Optogenetic activation of orexin neurons in lateral hypothalamus or orexinergic fibers innervating raphe pallidus impaired or improved glucose tolerance, respectively. Collectively, the present study assigns orexin signaling in serotonergic neurons critical, yet differential orexin receptor type 1- and 2-dependent functions in the regulation of systemic glucose homeostasis.

scholarly journals MiR-206 is expressed in pancreatic islets and regulates glucokinase activity

2016 ◽  
Vol 311 (1) ◽  
pp. E175-E185 ◽  
Author(s):  
Manjula Vinod ◽  
Jay V. Patankar ◽  
Vinay Sachdev ◽  
Saša Frank ◽  
Wolfgang F. Graier ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Pancreatic Islets ◽  
Glucose Homeostasis ◽  
Posttranscriptional Regulation ◽  
Germ Line ◽  
In Silico Analysis ◽  
Liver Glycogen ◽  
Whole Body ◽  
The Metabolic Syndrome

Glucose homeostasis is a complex indispensable process, and its dysregulation causes hyperglycemia and type 2 diabetes mellitus. Glucokinase (GK) takes a central role in these pathways and is thus rate limiting for glucose-stimulated insulin secretion (GSIS) from pancreatic islets. Several reports have described the transcriptional regulation of Gck mRNA, whereas its posttranscriptional mechanisms of regulation, especially those involving microRNAs (miR), are poorly understood. In this study, we investigated the role of miR-206 as a posttranscriptional regulator of Gck. In addition, we examined the effects of miR-206 on glucose tolerance, GSIS, and gene expression in control and germ line miR-206 knockout (KO) mice fed either with chow or high-fat diet (HFD). MiR-206 was found in Gck-expressing tissues and was differentially altered in response to HFD feeding. Pancreatic islets showed the most profound induction in the expression of miR-206 in response to HFD. Chow- and HFD-fed miR-206KO mice have improved glucose tolerance and GSIS but unaltered insulin sensitivity. In silico analysis of Gck mRNA revealed a conserved 8-mer miR-206 binding site. Hence, the predicted regulation of Gck by miR-206 was confirmed in reporter and GK activity assays. Concomitant with increased GK activity, miR-206KO mice had elevated liver glycogen content and plasma lactate concentrations. Our findings revealed a novel mechanism of posttranscriptional regulation of Gck by miR-206 and underline the crucial role of pancreatic islet miR-206 in the regulation of whole body glucose homeostasis in a murine model that mimics the metabolic syndrome.

The Effect of Handcycle Ergometer Exercise on Glucose Tolerance in Ambulatory and Non-Ambulatory Adolescents

2017 ◽  
Vol 29 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Kevin R. Short ◽  
April M. Teague ◽  
Jake C. Klein ◽  
Elizabeth Malm-Buatsi ◽  
Dominic Frimberger
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Upper Body ◽  
Whole Body ◽  
Control Group ◽  
Mobility Limitations ◽  
Upper Body Exercise ◽  
Significant Group ◽  
Ergometer Exercise ◽  
The Impact

Purpose:Whole body or leg exercise before a meal can increase insulin sensitivity, but it is unclear whether the same can occur with upper body exercise since a smaller muscle mass is activated. We measured the impact of a single session of handcycle exercise on glucose tolerance and insulin sensitivity.Methods:Nonambulatory (Non-Amb) adolescents with spina bifida or cerebral palsy (4F/3M), or ambulatory peers (Control, 4F/7M) completed 2 glucose tolerance tests on separate days, preceded by either rest or a 35-min bout of moderate-to-vigorous intermittent handcycle exercise.Results:The Non-Amb group had higher body fat (mean ± SD: 38 ± 12%, Control: 24 ± 9, p = .041) but similar VO2peak (17.7 ± 6.1 ml/kg/min, Control: 21.1 ± 7.9). Fasting glucose and insulin were normal for all participants. Compared with the rest trial, exercise resulted in a reduction in glucose area under the curve (11%, p = .008) without a significant group x trial interaction and no difference in the magnitude of change between groups. Insulin sensitivity was increased 16% (p = .028) by exercise in the Control group but was not significantly changed in the Non-Amb group.Conclusion:A single bout of handcycle exercise improves glucose tolerance in adolescents with and without mobility limitations and could therefore help maintain or improve metabolic health.

Whole-body skeletal muscle mass is not related to glucose tolerance or insulin sensitivity in overweight and obese men and women

2008 ◽  
Vol 33 (4) ◽  
pp. 769-774 ◽  
Author(s):  
Jennifer L. Kuk ◽  
Katherine Kilpatrick ◽  
Lance E. Davidson ◽  
Robert Hudson ◽  
Robert Ross
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Muscle Mass ◽  
Visceral Adipose Tissue ◽  
Skeletal Muscle Mass ◽  
Whole Body ◽  
Men And Women ◽  
Visceral Adipose

The relationship between skeletal muscle mass, visceral adipose tissue, insulin sensitivity, and glucose tolerance was examined in 214 overweight or obese, but otherwise healthy, men (n = 98) and women (n = 116) who participated in various exercise and (or) weight-loss intervention studies. Subjects had a 75 g oral glucose tolerance test and (or) insulin sensitivity measures by a 3 h hyperinsulinemic–euglycemic clamp technique. Whole-body skeletal muscle mass and visceral adipose tissue were measured using a multi-slice magnetic resonance imaging protocol. Total body skeletal muscle mass was not associated with any measure of glucose metabolism in men or women (p > 0.10). These observations remained independent of age and total adiposity. Conversely, visceral adipose tissue was a significant predictor of various measures of glucose metabolism in both men and women with or without control for age and (or) total body fat (p < 0.05). Although skeletal muscle is a primary site for glucose uptake and deposition, these findings suggest that unlike visceral adipose tissue, whole-body skeletal muscle mass per se is not associated with either glucose tolerance or insulin sensitivity in overweight and obese men and women.

Effect of metformin on substrate utilization after exercise training in adults with impaired glucose tolerance

2013 ◽  
Vol 38 (4) ◽  
pp. 427-430 ◽  
Author(s):  
Steven K. Malin ◽  
Barry Braun
Keyword(s):  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Oxygen Uptake ◽  
Indirect Calorimetry ◽  
Substrate Utilization ◽  
Peak Oxygen Uptake ◽  
Whole Body ◽  
Glucose Kinetics

Metformin attenuates the higher insulin sensitivity that occurs with exercise training. Sixteen people with prediabetes trained for 10 weeks while taking metformin (n = 8) or placebo (n = 8). Substrate utilization was assessed using glucose kinetics and indirect calorimetry. After training, exercise whole-body fat oxidation was higher and glycogen use lower (p < 0.05), with no differences between groups. Blood glucose use was unchanged. Training-induced enhancement of insulin sensitivity (clamp) correlated with higher peak oxygen uptake (r = 0.70; p < 0.05), but was independent of glucose kinetic and substrate metabolism.

scholarly journals Incorporation of Fatty Acids as a Biomarker of Dietary Intake and Source is Fatty Acid and Blood Fraction Specific in CD-1 Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 483-483
Author(s):  
Allison Unger ◽  
Thomas Jetton ◽  
Emily Bono ◽  
James Whitley ◽  
Jana Kraft
Keyword(s):  
Fatty Acid ◽  
Fish Oil ◽  
Assessment Tool ◽  
Vaccenic Acid ◽  
Plasma Cholesterol ◽  
Stearidonic Acid ◽  
Gas Liquid Chromatography ◽  
Echium Oil ◽  
Dairy Fat ◽  
Blood Fraction

Abstract Objectives Accurate biomarkers of fatty acid (FA) intake and source (e.g., diet-derived FA) are an important assessment tool to study the role of dietary fat quality on metabolic health. The purpose of this study was to assess the incorporation of unique, dietary FA from fish oil, echium oil, and dairy fat into the red blood cell membranes (RBCM), plasma phospholipids (PPL), and plasma cholesterol esters (PCE) of genetically-outbred CD-1 mice. Methods At one month of age, mice were assigned to one of four isocaloric diets consisting either of a control fat blend or the control fat blend supplemented (30%) with fish oil, echium oil, or dairy fat (n = 10/diet/sex). After 52 weeks of feeding, cardiac blood was collected for FA analysis of RBCM, PPL, and PCE using gas-liquid chromatography. Results Expectedly, a higher proportion of fish-derived FA (eicosapentaenoic acid and docosahexaenoic acid) was observed in the RBCM and PCE of fish oil-fed mice (P &lt; 0.0001). Accordingly, a greater proportion of echium oil-derived γ-linolenic acid was incorporated into all blood fractions of echium oil-fed mice (P &lt; 0.0001). Yet, stearidonic acid, specific to echium oil, was not detected in the RBCM of mice, and no differences in the proportion of stearidonic acid were found in the PPL and PCE. Odd-chain FA (pentadecanoic acid and heptadecanoic acid) were not exclusively enriched in the blood fractions of dairy-fed mice. Conversely, trans-palmitoleic acid, vaccenic acid, rumenic acid, and branched-chain FA were differentially incorporated into the PPL and PCE, while not detected in the RBCM. Conclusions In summary, unique, diet-derived FA are differentially incorporated into the blood fractions of mice, indicating that the incorporation of dietary FA into blood fractions is highly dependent upon the FA species. Therefore, diet-derived FA cannot be used universally as a reliable biomarker to validate dietary FA source in mice, rather, the specific FA and blood fraction must be carefully considered. Funding Sources Armin Grams Memorial Research Award, UVM Robert Larner, M.D. College of Medicine; USDA-NIFA Hatch Fund (accession number: 1,006,628).

scholarly journals Adipocyte Gi signaling is essential for maintaining whole-body glucose homeostasis and insulin sensitivity

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Lei Wang ◽  
Sai P. Pydi ◽  
Lu Zhu ◽  
Luiz F. Barella ◽  
Yinghong Cui ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Whole Body

scholarly journals SUN-670 P300 and CBP Are Necessary for Skeletal Muscle Insulin-Stimulated Glucose Uptake

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Vitor Fernandes Martins ◽  
Samuel LaBarge ◽  
Kristoffer Svensson ◽  
Jennifer M Cunliffe ◽  
Dion Banoian ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Uptake ◽  
Ex Vivo ◽  
Binding Protein ◽  
Whole Body ◽  
Oral Glucose ◽  
Skeletal Muscle Insulin Sensitivity

Abstract Introduction: Akt is a critical mediator of insulin-stimulated glucose uptake in skeletal muscle. The acetyltransferases, E1A binding protein p300 (p300) and cAMP response element-binding protein binding protein (CBP) are phosphorylated and activated by Akt, and p300/CBP can acetylate and inactivate Akt, thus giving rise to a possible Akt-p300/CBP axis. Our objective was to determine the importance of p300 and CBP to skeletal muscle insulin sensitivity. Methods: We used Cre-LoxP methodology to generate mice with a tamoxifen-inducible, conditional knock out of Ep300 and/or Crebbp in skeletal muscle. At 13-15 weeks of age, the knockout was induced via oral gavage of tamoxifen and oral glucose tolerance, ex vivo skeletal muscle insulin sensitivity, and microarray and proteomics analysis were done. Results: Loss of both p300 and CBP in adult mouse skeletal muscle rapidly and severely impairs whole body glucose tolerance and skeletal muscle insulin sensitivity. Furthermore, giving back a single allele of either p300 or CBP rescues both phenotypes. Moreover, the severe insulin resistance in the p300/CBP double knockout mice is accompanied by significant changes in both mRNA and protein expression of transcript/protein networks critical for insulin signaling, GLUT4 trafficking, and metabolism. Lastly, in human skeletal muscle samples, p300 and CBP protein levels correlate significantly and negatively with markers of insulin resistance. Conclusions: p300 and CBP are jointly required for maintaining whole body glucose tolerance and insulin sensitivity in skeletal muscle.

scholarly journals Effects of birth weight, sex and neonatal glucocorticoid overexposure on glucose–insulin dynamics in young adult horses

2016 ◽  
Vol 8 (2) ◽  
pp. 206-215 ◽  
Author(s):  
O. A. Valenzuela ◽  
J. K. Jellyman ◽  
V. L. Allen ◽  
N. B. Holdstock ◽  
A. J. Forhead ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Birth Weight ◽  
Insulin Sensitivity ◽  
Young Adult ◽  
Glucose Tolerance ◽  
Metabolic Phenotype ◽  
Whole Body ◽  
Sexually Dimorphic ◽  
Genetic And Environmental Factors ◽  
Glucose Stimulated Insulin Secretion

In several species, adult metabolic phenotype is influenced by the intrauterine environment, often in a sex-linked manner. In horses, there is also a window of susceptibility to programming immediately after birth but whether adult glucose–insulin dynamics are altered by neonatal conditions remains unknown. Thus, this study investigated the effects of birth weight, sex and neonatal glucocorticoid overexposure on glucose–insulin dynamics of young adult horses. For the first 5 days after birth, term foals were treated with saline as a control or ACTH to raise cortisol levels to those of stressed neonates. At 1 and 2 years of age, insulin secretion and sensitivity were measured by exogenous glucose administration and hyperinsulinaemic–euglycaemic clamp, respectively. Glucose-stimulated insulin secretion was less in males than females at both ages, although there were no sex-linked differences in glucose tolerance. Insulin sensitivity was greater in females than males at 1 year but not 2 years of age. Birth weight was inversely related to the area under the glucose curve and positively correlated to insulin sensitivity at 2 years but not 1 year of age. In contrast, neonatal glucocorticoid overexposure induced by adrenocorticotropic hormone (ACTH) treatment had no effect on whole body glucose tolerance, insulin secretion or insulin sensitivity at either age, although this treatment altered insulin receptor abundance in specific skeletal muscles of the 2-year-old horses. These findings show that glucose–insulin dynamics in young adult horses are sexually dimorphic and determined by a combination of genetic and environmental factors acting during early life.

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