Lupin protein isolate improves insulin sensitivity and steatohepatitis in vivo and modulates the expression of the Fasn , Gys2 , and Gsk3b genes

Differences in gender are in part responsible for the development of insulin resistance (IR) and associated hypertension. Currently, it is unclear whether these differences are dictated by gender itself or by the relative changes in plasma estrogen and/or testosterone. We investigated the interrelationships between testosterone and estrogen in the progression of IR and hypertension in vivo in intact and gonadectomized fructose-fed male rats. Treatment with estrogen significantly reduced the testosterone levels in both normal chow-fed and fructose-fed rats. Interestingly, fructose feeding induced a relative increase in estradiol levels, which did not affect IR in both intact and gonadectomized fructose-fed rats. However, increasing the estrogen levels improved insulin sensitivity in both intact and gonadectomized fructose-fed rats. In intact males, fructose feeding increased the blood pressure (140 ± 2 mmHg), which was prevented by estrogen treatment. However, the blood pressure in the fructose-fed estrogen rats (125 ± 1 mmHg) was significantly higher than that of normal chow-fed (113 ± 1 mmHg) and fructose-fed gonadectomized rats. Estrogen treatment did not affect the blood pressure in gonadectomized fructose-fed rats (105 ± 2 mmHg). These data suggest the existence of a threshold value for estrogen below which insulin sensitivity is unaffected. The development of hypertension in this model is dictated solely by the presence or absence of testosterone. In summary, the development of IR and hypertension is governed not by gender per se but by the interactions of specific sex hormones such as estrogen and testosterone.

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

Prep1 Deficiency Induces Protection from Diabetes and Increased Insulin Sensitivity through a p160-Mediated Mechanism

Molecular and Cellular Biology ◽

10.1128/mcb.00117-08 ◽

2008 ◽

Vol 28 (18) ◽

pp. 5634-5645 ◽

Cited By ~ 35

Author(s):

Francesco Oriente ◽

Luis Cesar Fernandez Diaz ◽

Claudia Miele ◽

Salvatore Iovino ◽

Silvia Mori ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Glucose Uptake ◽

Normal Glucose Tolerance ◽

Glucose Disposal ◽

Protein Levels ◽

Normal Glucose ◽

Enhanced Expression ◽

The Stability

ABSTRACT We have examined glucose homeostasis in mice hypomorphic for the homeotic transcription factor gene Prep1. Prep1-hypomorphic (Prep1 i / i ) mice exhibit an absolute reduction in circulating insulin levels but normal glucose tolerance. In addition, these mice exhibit protection from streptozotocin-induced diabetes and enhanced insulin sensitivity with improved glucose uptake and insulin-dependent glucose disposal by skeletal muscle. This muscle phenotype does not depend on reduced expression of the known Prep1 transcription partner, Pbx1. Instead, in Prep1 i / i muscle, we find normal Pbx1 but reduced levels of the recently identified novel Prep1 interactor p160. Consistent with this reduction, we find a muscle-selective increase in mRNA and protein levels of PGC-1α, accompanied by enhanced expression of the GLUT4 transporter, responsible for insulin-stimulated glucose uptake in muscle. Indeed, using L6 skeletal muscle cells, we induced the opposite effects by overexpressing Prep1 or p160, but not Pbx1. In vivo skeletal muscle delivery of p160 cDNA in Prep1 i / i mice also reverses the molecular phenotype. Finally, we show that Prep1 controls the stability of the p160 protein. We conclude that Prep1 controls insulin sensitivity through the p160-GLUT4 pathway.

Download Full-text

Effects of prolonged Acipimox treatment on glucose and lipid metabolism and on in vivo insulin sensitivity in patients with non-insulin dependent diabetes mellitus

Acta Endocrinologica ◽

10.1530/acta.0.1270344 ◽

1992 ◽

Vol 127 (4) ◽

pp. 344-350 ◽

Cited By ~ 32

Author(s):

Allan A Vaag ◽

Henning Beck-Nielsen

Keyword(s):

Lipid Metabolism ◽

Insulin Sensitivity ◽

Treatment Period ◽

Blood Glucose Control ◽

Glucose Disposal ◽

Prolonged Treatment ◽

Double Blind Study ◽

Glucose And Lipid Metabolism ◽

Fasting Plasma

The effect of prolonged treatment with Acipimox on in vivo peripheral insulin sensitivity, and on glucose and lipid metabolism, was investigated in patients with NIDDM in a double-blind study. Twelve NIDDM patients were randomized to treatment with either placebo or Acipimox in pharmacological doses (250 mg×3) for three months. Fasting plasma glucose, insulin, C-peptide and HbA1c concentrations were unaffected after three months of acipimox treatment. However, fasting plasma non-esterifled fatty acid (NEFA) concentrations were twofold elevated after Acipimox treatment (1.34±0.09 vs 0.66±0.09 mmol/l; p<0.05). Despite this, repeated acute Acipimox administration after the three months' treatment period enhanced total insulin-stimulated glucose disposal to the same extent as acute Acipimox administration before the treatment period (367±59 vs 392±66 mg·m−2·min−1, NS; both p<0.05 vs placebo glucose disposal) (267±44 mg·m−2·min−1). In conclusion, insulin resistance or tachyphylaxis towards the effects of Acipimox on insulin stimulated glucose disposal was not induced during prolonged Acipimox treatment. The lack of improvement of blood glucose control in the patients with NIDDM may be due to the demonstrated rebound effect of lipolysis.

Download Full-text

ALY688 elicits adiponectin-mimetic signaling and improves insulin action in skeletal muscle cells

AJP Cell Physiology ◽

10.1152/ajpcell.00603.2020 ◽

2021 ◽

Author(s):

Hye Kyoung Sung ◽

Patricia L. Mitchell ◽

Sean Gross ◽

Andre Marette ◽

Gary Sweeney

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Glucose Uptake ◽

Glucose Transporter ◽

Muscle Cells ◽

Temporal Analysis ◽

Skeletal Muscle Cells ◽

Adiponectin Receptor ◽

Metabolic Effects

Adiponectin is well established to mediate many beneficial metabolic effects, and this has stimulated great interest in development and validation of adiponectin receptor agonists as pharmaceutical tools. This study investigated the effects of ALY688, a peptide-based adiponectin receptor agonist, in rat L6 skeletal muscle cells. ALY688 significantly increased phosphorylation of several adiponectin downstream effectors, including AMPK, ACC and p38MAPK, assessed by immunoblotting and immunofluorescence microscopy. Temporal analysis using cells expressing an Akt biosensor demonstrated that ALY688 enhanced insulin sensitivity. This effect was associated with increased insulin-stimulated Akt and IRS-1 phosphorylation. The functional metabolic significance of these signaling effects was examined by measuring glucose uptake in myoblasts stably overexpressing the glucose transporter GLUT4. ALY688 treatment both increased glucose uptake itself and enhanced insulin-stimulated glucose uptake. In the model of high glucose/high insulin (HGHI)-induced insulin resistant cells, both temporal studies using the Akt biosensor as well as immunoblotting assessing Akt and IRS-1 phosphorylation indicated that ALY688 significantly reduced insulin resistance. Importantly, we observed that ALY688 administration to high-fat high sucrose fed mice also improve glucose handling, validating its efficacy in vivo. In summary, these data indicate that ALY688 activates adiponectin signaling pathways in skeletal muscle, leading to improved insulin sensitivity and beneficial metabolic effects.

Download Full-text

Potensi Hipolipidemik Yogurt dari Isolat Protein Biji Kecipir (Psophocarpus tetragonolobus) pada Tikus Hiperkolesterol dengan Perlakuan Jumlah Pakan

Jurnal Agritech ◽

10.22146/agritech.16994 ◽

2017 ◽

Vol 37 (1) ◽

pp. 1

Author(s):

Agus Slamet ◽

Bayu Kanetro

Keyword(s):

High Density Lipoprotein ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Protein Isolate ◽

High Density ◽

Winged Bean ◽

Low Density ◽

Sprague Dawley ◽

High Concentration

Protein content of winged bean is almost the same as soybean, but the beany flavor is more poweful than soybean. Therefore the protein of winged bean was isolated prior to use as raw material of yogurt. This research was aimed to determine the potency of hypocholestrolemic activity of yogurt protein isolate of winged bean through in vivo bioassay by using Sprague Dawley male rats. The treatments of the research were yogurt feed treatment with concentration of yogurt 0 (standard feed without yogurt as a control), 2, and 4 g yogurt/day as low and high concentration treatment respectively for 4th weeks after hypercholesterol feed treatment for 1 week. The blood lipid profile of rats, including triglyceride, cholesterol total, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) cholesterol were analysed on the 2nd and 4th weeks for the yogurt feed treatment while for before yogurt feed treatment, the evaluation were based on the adaptation phase and the 1st week for hypercholesterol phase. The result of this research showed that the blood triglyceride, cholesterol total, LDL increased, and the blood HDL decreased in hypercholesterol phase before yogurt feed treatment. The potency of hypocholestrolemic of yogurt from protein isolate of winged bean was shown by the decreasing of blood triglyceride, cholesterol total, LDL and increasing the HDL cholesterol after the yogurt feed treatment with low and high concentration. That indicated that yogurt that was made of protein isolate of winged bean could reduced cholesterol. ABSTRAKBiji kecipir memiliki kadar protein yang hampir sama dengan kedelai, namun bau langunya lebih tajam daripada kedelai, sehingga perlu diisolasi proteinnya sebelum digunakan sebagai bahan baku yogurt. Tujuan penelitian ini adalah menentukan potensi hipokolesterolemik yogurt isolat proteun biji kecipir melalui uji biologis in vivo menggunakan tikus jantan Sprague Dawley. Perlakuan penelitian ini adalah perlakuan pakan yogurt dengan konsentrasi 0 (pakan standar tanpa penambahan yogurt sebagai kontrol), 2, dan 4 g yogurt/hari berturut-turut sebagai perlakuan konsentrasi rendah dan tinggi selama 4 minggu perlakuan pakan yogurt sesudah pemberian pakan hiperkolesterol selama 1 minggu. Profil lipida darah tikus meliputi kadar trigliserida, total kolesterol, kolesterol High Density Lipoprotein (HDL), dan Low Density Lipoprotein (LDL) dianalisis pada minggu ke 2 dan 4 minggu selama perlakuan pakan yogurt dan sebelum perlakuan pakan yogurt yaitu pada fase pemeliharaan adaptasi dan 1 minggu pada fase pemeliharan hiperkolesterol. Hasil penelitian ini menunjukkan bahwa trigliserida, total kolesterol, dan kolesterol LDL meningkat dan kolesterol HDL menurun selama fase pemberian pakan hiperkolesterol sebelum perlakuan pakan yogurt. Potensi hipokolesterol yogurt isolat protein biji kecipir ditunjukkan dengan penurunan trigliserida, total kolesterol, dan kolesterol LDL, serta peningkatan kolesterol HDL sesudah perlakuan pakan yogurt dengan konsentrasi rendah maupun tinggi. Hal tersebut mengindikasikan bahwa yogurt isolat protein biji kecipir mampu menurunkan kolesterol.

Download Full-text

Follow-up of GK rats during prediabetes highlights increased insulin action and fat deposition despite low insulin secretion

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00501.2007 ◽

2008 ◽

Vol 294 (1) ◽

pp. E168-E175 ◽

Cited By ~ 32

Author(s):

Jamileh Movassat ◽

Danièle Bailbé ◽

Cécile Lubrano-Berthelier ◽

Françoise Picarel-Blanchot ◽

Eric Bertin ◽

...

Keyword(s):

Body Composition ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Cell Function ◽

Cell Mass ◽

The Body ◽

Whole Body ◽

Β Cell ◽

Gk Rats

The adult Goto-Kakizaki (GK) rat is characterized by impaired glucose-induced insulin secretion in vivo and in vitro, decreased β-cell mass, decreased insulin sensitivity in the liver, and moderate insulin resistance in muscles and adipose tissue. GK rats do not exhibit basal hyperglycemia during the first 3 wk after birth and therefore could be considered prediabetic during this period. Our aim was to identify the initial pathophysiological changes occurring during the prediabetes period in this model of type 2 diabetes (T2DM). To address this, we investigated β-cell function, insulin sensitivity, and body composition in normoglycemic prediabetic GK rats. Our results revealed that the in vivo secretory response of GK β-cells to glucose is markedly reduced and the whole body insulin sensitivity is increased in the prediabetic GK rats in vivo. Moreover, the body composition of suckling GK rats is altered compared with age-matched Wistar rats, with an increase of the number of adipocytes before weaning despite a decreased body weight and lean mass in the GK rats. None of these changes appeared to be due to the postnatal nutritional environment of GK pups as demonstrated by cross-fostering GK pups with nondiabetic Wistar dams. In conclusion, in the GK model of T2DM, β-cell dysfunction associated with increased insulin sensitivity and the alteration of body composition are proximal events that might contribute to the establishment of overt diabetes in adult GK rats.

Download Full-text