Enzymatic digest of whey protein and wheylin-1, a dipeptide released in the digest, increase insulin sensitivity in an Akt phosphorylation-dependent manner

2018 ◽  
Vol 9 (9) ◽  
pp. 4635-4641 ◽  
Author(s):  
Maiko Ogiwara ◽  
Wakana Ota ◽  
Takafumi Mizushige ◽  
Ryuhei Kanamoto ◽  
Kousaku Ohinata
Keyword(s):  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Whey Protein ◽  
Dependent Manner ◽  
Increase Insulin Sensitivity ◽  
Akt Phosphorylation ◽  
Glucose Levels ◽  
Blood Glucose Levels

Wheylin-1 is the first whey-derived peptide that increases insulin sensitivity in an Akt phosphorylation-dependent manner and lowers blood glucose levels.

scholarly journals Vanadyl Sulfate Treatment Stimulates Proliferation and Regeneration of Beta Cells in Pancreatic Islets

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Samira Missaoui ◽  
Khémais Ben Rhouma ◽  
Mohamed-Tahar Yacoubi ◽  
Mohsen Sakly ◽  
Olfa Tebourbi
Keyword(s):  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Pancreatic Islets ◽  
Beta Cells ◽  
Control Level ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Dependent Manner ◽  
Glucose Levels ◽  
Blood Glucose Levels

We examined the effects of vanadium sulfate (VOSO4) treatment at 5 and 10 mg/kg for 30 days on endocrine pancreas activity and histology in nondiabetic and STZ-induced diabetic rats. In diabetic group, blood glucose levels significantly increased while insulinemia level markedly decreased. At the end of treatment, VOSO4at a dose of 10 mg/Kg normalized blood glucose level in diabetic group, restored insulinemia, and significantly improved insulin sensitivity. VOSO4also increased in a dose-dependent manner the number of insulin immunopositive beta cells in pancreatic islets of nondiabetic rats. Furthermore, in the STZ-diabetic group, the decrease in the number of insulin immunopositive beta cells was corrected to reach the control level mainly with the higher dose of vanadium. Therefore, VOSO4treatment normalized plasma glucose and insulin levels and improved insulin sensitivity in STZ-experimental diabetes and induced beta cells proliferation and/or regeneration in normal or diabetic rats.

scholarly journals MON-613 The Expression of TBC1 Domain Family, Member 4 (TBC1D4) in Skeletal Muscles of Insulin-Resistant Mice in Response to Sulforaphane

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nasser M Rizk ◽  
Amina Saleh ◽  
Abdelrahman ElGamal ◽  
Dina Elsayegh ◽  
Isin Cakir ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Skeletal Muscles ◽  
Glucose Disposal ◽  
Domain Family ◽  
Insulin Resistant ◽  
Glucose Levels ◽  
Blood Glucose Levels

Abstract The Expression of TBC1 Domain Family, member 4 (TBC1D4) in Skeletal Muscles of Insulin-Resistant Mice in Response to Sulforaphane. Background: Obesity is commonly accompanied by impaired glucose homeostasis. Decreased glucose transport to the peripheral tissues, mainly skeletal muscle, leads to reduced total glucose disposal and hyperglycemia. TBC1D4 gene is involved in the trafficking of GLUT4 to the outer cell membrane in skeletal muscle. Sulforaphane (SFN) has been suggested as a new potential anti-diabetic compound acting by reducing blood glucose levels through mechanisms not fully understood (1). The aim of this study is to investigate the effects SFN on TBC1D4 and GLUT4 gene expression in skeletal muscles of DIO mice, in order to elucidate the mechanism(s) through which SFN improves glucose homeostasis. Methodology: C57BL/6 mice (n=20) were fed with a high fat diet (60%) for 16 weeks to generate diet induced obese (DIO) mice with body weights between 45–50 gm. Thereafter, DIO mice received either SFN (5mg/kg BW) (n=10) or vehicle (n=10) as controls daily by intraperitoneal injections for four weeks. Glucose tolerance test (1g/kg BW, IP) and insulin sensitivity test (ITT) were conducted (1 IU insulin/ g BW, IP route) at the beginning and end of the third week of the injection. At the end of 4 weeks of the injection, samples of blood and skeletal muscles of both hindlimbs were collected. The expression levels of GLUT4 and TBC1D4 genes were analyzed by qRT-PCR. Blood was also used for glucose, adiponectin and insulin measurements. Results: SFN-treated DIO mice had significantly lower non-fasting blood glucose levels than vehicle-treated mice (194.16 ± 14.12 vs. 147.44 ± 20.31 mg/dL, vehicle vs. SFN, p value=0.0003). Furthermore, GTT results indicate that the blood glucose levels at 120 minutes after glucose infusion in was (199.83±34.53 mg/dl vs. 138.55±221.78 mg/dl) for vehicle vs. SFN with p=0.0011 respectively. ITT showed that SFN treatment did not enhance insulin sensitivity in DIO mice. Additionally, SFN treatment did not significantly change the expression of TBC1D4, and GLUT4 genes in skeletal muscles compared to vehicle treatment (p values >0.05). Furthermore, SFN treatment did not significantly affect the systemic insulin (1.84±0.74 vs 1.54±0.55 ng/ml, p=0.436), or adiponectin (11.96 ±2.29 vs 14.4±3.33 ug/ml, p=0.551) levels in SFN vs. vehicle-treated DIO mice, respectively. Conclusion: SFN treatment improves glucose disposal in DIO mice, which is not linked to the gene expression of GLUT4 and TBC1D4 and its mechanism of glucose disposal in skeletal muscles. Furthermore, SFN treatment did not improve insulin level, and the insulin sensitizer hormone adiponectin as potential players for enhancing insulin sensitivity. 1. Axelsson AS, Tubbs E, Mecham B, Chacko S, Nenonen HA, Tang Y, et al. Sci Transl Med. 2017;9(394).

scholarly journals Effect of Glucose on Recovery of Energy Metabolism following Hypoxia—Oligemia in Mouse Brain: Dose-Dependence and Carbohydrate Specificity

1983 ◽  
Vol 3 (4) ◽  
pp. 486-492 ◽  
Author(s):  
Frank A. Welsh ◽  
Renee E. Sims ◽  
Ann E. McKee
Keyword(s):  
Blood Glucose ◽  
Energy Metabolism ◽  
Cerebral Metabolism ◽  
Dose Dependence ◽  
Poor Correlation ◽  
Dependent Manner ◽  
Tissue Samples ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Effect Of Glucose

Unilateral cerebral hypoxia–oligemia was produced in anesthetized mice using carotid artery occlusion combined with systemic hypoxia (10% O2). In the cerebral cortex ipsilateral to the carotid occlusion, ATP levels were depleted during a 30-min insult, but were restored to 64% of control during 60 min of recovery. Pretreatment of animals with glucose diminished the restoration of ATP in a dose-dependent manner. Thus, when blood glucose levels exceeded 12–13 m M (225 mg/dl), ATP recovery was greatly impaired. Neither galactose nor 3- O-methylglucose mimicked the detrimental effect of glucose. However, pretreatment with mannose, which is readily metabolized by brain, impaired restoration of ATP. The impairment, therefore, appears to be specific for substrates of cerebral metabolism. The ischemic accumulation of lactate in the ipsilateral cortex was augmented by only 30% at blood glucose levels well above the threshold for ATP recovery. Thus, unless recovery of energy metabolism is sensitive to small increments in brain lactate, it is difficult to explain the glucose-induced energy failure on the basis of enhanced lactic acidosis. Ipsilateral cerebral blood flow (CBF), measured with [14C]iodoantipyrine during hypoxia and recovery, was lower in glucose-pretreated than in saline-pretreated animals. However, the poor correlation between CBF and ATP, measured in the same tissue samples at 15 min recovery, failed to substantiate that regeneration of ATP was flow-limited early in recovery.

scholarly journals Suppression of Prolactin Secretion Partially Explains the Antidiabetic Effect of Bromocriptine in ob/ob Mice

Endocrinology ◽  
2018 ◽  
Vol 160 (1) ◽  
pp. 193-204 ◽  
Author(s):  
Isadora C Furigo ◽  
Miriam F Suzuki ◽  
João E Oliveira ◽  
Angela M Ramos-Lobo ◽  
Pryscila D S Teixeira ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Prolactin Secretion ◽  
Dopamine Receptor Agonist ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Insulin Tolerance ◽  
Promising Therapeutic Approach

Abstract Previous studies have shown that bromocriptine mesylate (Bromo) lowers blood glucose levels in adults with type 2 diabetes mellitus; however, the mechanism of action of the antidiabetic effects of Bromo is unclear. As a dopamine receptor agonist, Bromo can alter brain dopamine activity affecting glucose control, but it also suppresses prolactin (Prl) secretion, and Prl levels modulate glucose homeostasis. Thus, the objective of the current study was to investigate whether Bromo improves insulin sensitivity via inhibition of Prl secretion. Male and female ob/ob animals (a mouse model of obesity and insulin resistance) were treated with Bromo and/or Prl. Bromo-treated ob/ob mice exhibited lower serum Prl concentration, improved glucose and insulin tolerance, and increased insulin sensitivity in the liver and skeletal muscle compared with vehicle-treated mice. Prl replacement in Bromo-treated mice normalized serum Prl concentration without inducing hyperprolactinemia. Importantly, Prl replacement partially reversed the improvements in glucose homeostasis caused by Bromo treatment. The effects of the Prl receptor antagonist G129R-hPrl on glucose homeostasis were also investigated. We found that central G129R-hPrl infusion increased insulin tolerance of male ob/ob mice. In summary, our findings indicate that part of Bromo effects on glucose homeostasis are associated with decrease in serum Prl levels. Because G129R-hPrl treatment also improved the insulin sensitivity of ob/ob mice, pharmacological compounds that inhibit Prl signaling may represent a promising therapeutic approach to control blood glucose levels in individuals with insulin resistance.

scholarly journals Increased basal level of Akt-dependent insulin signaling may be responsible for the development of insulin resistance

2009 ◽  
Vol 297 (4) ◽  
pp. E898-E906 ◽  
Author(s):  
Hui-Yu Liu ◽  
Tao Hong ◽  
Ge-Bo Wen ◽  
Jianmin Han ◽  
Degen Zuo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Insulin Signaling ◽  
Kinase Inhibitor ◽  
Phosphatidylinositol 3 Kinase ◽  
Akt Phosphorylation ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Triglyceride Content

A majority of subjects with insulin resistance and hyperinsulinemia can maintain their blood glucose levels normal for the whole life presumably through protein kinase B (Akt)-dependent insulin signaling. In this study, we found that the basal Akt phosphorylation level was increased in liver and gastrocnemius of mice under the high-fat diet (HFD). Levels of mitochondrial DNA and expression of some mitochondrion-associated genes were decreased by the HFD primarily in liver. Triglyceride content was increased in both liver and gastrocnemius by the HFD. Oxidative stress was induced by the HFD in both liver and gastrocnemius. Insulin sensitivity was decreased by the HFD. All of these changes were largely or completely reversed by treatment of animals with the phosphatidylinositol 3-kinase inhibitor LY-294002 during the time when animals usually do not eat. Consequently, the overall insulin sensitivity was increased by treatment with LY-294002. Together, our results indicate that increased basal Akt-dependent insulin signaling suppresses mitochondrial production, increases ectopic fat accumulation, induces oxidative stress, and desensitizes insulin signaling in subjects with insulin resistance and hyperinsulinemia.

Effect of consumption of a carob pod inositol-enriched beverage on insulin sensitivity and inflammation in middle-aged prediabetic subjects

2016 ◽  
Vol 7 (10) ◽  
pp. 4379-4387 ◽  
Author(s):  
Celia Bañuls ◽  
Susana Rovira-Llopis ◽  
Sandra López-Doménech ◽  
Silvia Veses ◽  
Víctor M. Víctor ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
Impaired Fasting Glucose ◽  
Fasting Glucose ◽  
Middle Aged ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Carob Pod

This study assessed the effects of an inositol-enriched beverage (IEB) on blood glucose levels and inflammation status in subjects with an impaired fasting glucose (IFG) state according to body mass index (BMI).

Activated Akt Is Associated with Hyperglycemia and Platelet Hyperactivity in a Mouse Model of Diabetes

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5360-5360
Author(s):  
Lin Lu ◽  
Donna Woulfe
Keyword(s):  
Blood Glucose ◽  
Mouse Model ◽  
Platelet Activation ◽  
Diabetic Patients ◽  
Type I ◽  
Platelet Activity ◽  
Akt Phosphorylation ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Fibrinogen Binding

Abstract Platelet hyperactivation has been reported in patients with both Type I and Type II diabetes mellitus and likely contributes to the increased prevalence of thrombotic complications in diabetic patients. However, the mechanisms leading to platelet hyperactivity in diabetes are not fully understood. Our previous studies showed that the Akt signaling pathway positively regulates platelet activity. Here, we evaluate the effect of hyperglycemia on Akt phosphorylation and platelet activation using a Type I diabetic mouse model. Hyperglycemia was induced by intraperitoneal injection of streptozotocin (STZ 50mg/kg for 5 days) in C57BL/6 mice. Blood glucose levels were elevated in 12 mice 4 weeks after STZ injection (mean ± SD: 410 ± 70 mg/ml) compared with 11 mice without STZ injection (212 ± 50 mg/ml). Platelets from hyperglycemic mice showed enhanced agonist-dependent aggregation (max % aggregation: 58% ± 10% in hyperglycemia versus 0% in normoglycemia at 0.6mM AYPGKF, n=3 each), fibrinogen binding (62.2% fibrinogen-bound cells ± 5.4% in hyperglycemic conditions versus 46.1% ± 16.3% in normoglycemia at 2mM AYPGKF) and P-selectin binding (42.1% cells with surface P-selectin ± 3.7% in hyperglycemic platelets, 25.3% ± 5.9% in normoglycemia at 2mM AYPGKF) compared with platelets from mice with normal glucose levels. The blood glucose levels were directly correlated with Alexafluor-fibrinogen binding (r=0.65, p=0.042) when platelets were stimulated with thrombin receptor agonist peptide AYPGKF (1.5mM), and also directly correlated with P-selectin surface exposure (r=0.95, p=0.003) after platelets were stimulated with 1.5mM AYPGKF. To determine whether the Akt pathway is involved in enhanced platelet activation in diabetes, we tested phosphorylation of Akt ser473 by immunoblotting. Akt phosphorylation of this residue was increased (35% ± 4%) in platelets from hyperglycemic mice compared with platelets from nondiabetic mice. In conclusion, platelets from hyperglycemic mice are more sensitive to PAR4 agonist-induced fibrinogen binding and P-selectin exposure compared with nondiabetic platelets. Enhanced activation of Akt in platelets under hyperglycemic conditions may play a role in platelet hyperactivation in diabetes.

scholarly journals Phytochemical and Hypoglycemic Evaluation of Alangium Salviifolium Root Extract

2011 ◽  
Vol 3 (2) ◽  
pp. 393-402 ◽  
Author(s):  
Ahad H. A. ◽  
Padmaja B. S ◽  
Yesupadam P ◽  
Guruprakash P ◽  
Sravanthi M ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Ethanolic Extract ◽  
Diabetic Rats ◽  
Control Group ◽  
Root Extract ◽  
Alcoholic Extract ◽  
Dependent Manner ◽  
Standard Drug ◽  
Glucose Levels ◽  
Blood Glucose Levels

.The main purpose of present study was to perform phytochemical screening and explore the anti-hyperglycaemic properties of Alangium salvifolium root extract in normal and alloxan induced diabetic rats. A. salvifolium root gave maximum extractive values of 6.4 % w/w with Ethanol and other parameters were within limits. The extract gave positive tests for phytosterols, triterpenes, flavonoids, carbohydrates and alkaloids. The ethanolic extract of A. salvifolium was found to be nearly as potent as tolbutamide in decreasing the blood glucose levels in normal fasting rats. In normal control group the percent reduction in blood glucose indicated that the extract is fast acting. The extract showed significant decrease in blood glucose, when compared with tolbutamide. The evaluated blood glucose levels in alloxan induced diabetic rats were significantly decreased up to 24th h compared to tolbutamide. A single oral administration of alcoholic extract at doses 100, 250 and 500 mg per kg produced a significant blood glucose reduction in a dose dependent manner in normal and diabetic rats. These data confirm the hypoglycaemic and anti-hyperglycaemic effect of alcoholic extract of A. salvifolium root in normal and diabetic rats respectively when compared with standard drug tolbutamide.Keywords: Alangium salvifolium; Ethanolic extract; Alloxan induced; Hypoglycaemic action.© 2011 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved.doi:10.3329/jsr.v3i2.7047                J. Sci. Res. 3 (2), 393-402 (2011)

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