scholarly journals Resistin and Type 2 Diabetes: Regulation of Resistin Expression by Insulin and Rosiglitazone and the Effects of Recombinant Resistin on Lipid and Glucose Metabolism in Human Differentiated Adipocytes

2003 ◽  
Vol 88 (12) ◽  
pp. 6098-6106 ◽  
Author(s):  
Philip G. McTernan ◽  
FFolliott M. Fisher ◽  
George Valsamakis ◽  
Rajkumar Chetty ◽  
Alison Harte ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Uptake ◽  
Protein Secretion ◽  
In Vitro Studies ◽  
Dependent Manner ◽  
Diabetes Status ◽  
Human Diabetes ◽  
Type 2 Diabetic

Abstract Resistin, an adipocyte secreted factor, has been suggested to link obesity with type 2 diabetes in rodent models, but its relevance to human diabetes remains uncertain. Although previous studies have suggested a role for this adipocytokine as a pathogenic factor, its functional effects, regulation by insulin, and alteration of serum resistin concentration by diabetes status remain to be elucidated. Therefore, the aims of this study were to analyze serum resistin concentrations in type 2 diabetic subjects; to determine the in vitro effects of insulin and rosiglitazone (RSG) on the regulation of resistin, and to examine the functional effects of recombinant human resistin on glucose and lipid metabolism in vitro. Serum concentrations of resistin were analyzed in 45 type 2 diabetic subjects and 34 nondiabetic subjects. Subcutaneous human adipocytes were incubated in vitro with insulin, RSG, and insulin in combination with RSG to examine effects on resistin secretion. Serum resistin was increased by approximately 20% in type 2 diabetic subjects compared with nondiabetic subjects (P = 0.004) correlating with C-reactive protein. No other parameters, including adiposity and fasting insulin levels, correlated with serum resistin in this cohort. However, in vitro, insulin stimulated resistin protein secretion in a concentration-dependent manner in adipocytes [control, 1215 ± 87 pg/ml (mean ± sem); 1 nm insulin, 1414.0 ± 89 pg/ml; 1 μm insulin, 1797 ± 107 pg/ml (P < 0.001)]. RSG (10 nm) reduced the insulin-mediated rise in resistin protein secretion (1 nm insulin plus RSG, 971 ± 35 pg/ml; insulin, 1 μm insulin plus RSG, 1019 ± 28 pg/ml; P < 0.01 vs. insulin alone). Glucose uptake was reduced after treatment with 10 ng/ml recombinant resistin and higher concentrations (P < 0.05). Our in vitro studies demonstrated a small, but significant, reduction in glucose uptake with human recombinant resistin in differentiated preadipocytes. In human abdominal sc adipocytes, RSG blocks the insulin-mediated release of resistin secretion in vitro. In conclusion, elevated serum resistin in human diabetes reflects the subclinical inflammation prevalent in type 2 diabetes. Our in vitro studies suggest a modest effect of resistin in reducing glucose uptake, and suppression of resistin expression may contribute to the insulin-sensitizing and glucose-lowering actions of the thiazolidinediones.

scholarly journals 1-Deoxysphingolipids, Early Predictors of Type 2 Diabetes, Compromise the Functionality of Skeletal Myoblasts

2021 ◽  
Vol 12 ◽  
Author(s):  
Duyen Tran ◽  
Stephen Myers ◽  
Courtney McGowan ◽  
Darren Henstridge ◽  
Rajaraman Eri ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Muscle Dysfunction ◽  
Dependent Manner

Metabolic dysfunction, dysregulated differentiation, and atrophy of skeletal muscle occur as part of a cluster of abnormalities associated with the development of Type 2 diabetes mellitus (T2DM). Recent interest has turned to the attention of the role of 1-deoxysphingolipids (1-DSL), atypical class of sphingolipids which are found significantly elevated in patients diagnosed with T2DM but also in the asymptomatic population who later develop T2DM. In vitro studies demonstrated that 1-DSL have cytotoxic properties and compromise the secretion of insulin from pancreatic beta cells. However, the role of 1-DSL on the functionality of skeletal muscle cells in the pathophysiology of T2DM still remains unclear. This study aimed to investigate whether 1-DSL are cytotoxic and disrupt the cellular processes of skeletal muscle precursors (myoblasts) and differentiated cells (myotubes) by performing a battery of in vitro assays including cell viability adenosine triphosphate assay, migration assay, myoblast fusion assay, glucose uptake assay, and immunocytochemistry. Our results demonstrated that 1-DSL significantly reduced the viability of myoblasts in a concentration and time-dependent manner, and induced apoptosis as well as cellular necrosis. Importantly, myoblasts were more sensitive to the cytotoxic effects induced by 1-DSL rather than by saturated fatty acids, such as palmitate, which are critical mediators of skeletal muscle dysfunction in T2DM. Additionally, 1-DSL significantly reduced the migration ability of myoblasts and the differentiation process of myoblasts into myotubes. 1-DSL also triggered autophagy in myoblasts and significantly reduced insulin-stimulated glucose uptake in myotubes. These findings demonstrate that 1-DSL directly compromise the functionality of skeletal muscle cells and suggest that increased levels of 1-DSL observed during the development of T2DM are likely to contribute to the pathophysiology of muscle dysfunction detected in this disease.

scholarly journals Transient Silencing of a Type IV P-Type ATPase,Atp10c, Results in Decreased Glucose Uptake in C2C12 Myotubes

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
S. E. Hurst ◽  
S. C. Minkin ◽  
J. Biggerstaff ◽  
M. S. Dhar
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Mapk Pathway ◽  
Specific Inhibitor ◽  
C2c12 Myotubes ◽  
Glucose Transporter 1 ◽  
Transfected Cells

Atp10cis a strong candidate gene for diet-induced obesity and type 2 diabetes. To identify molecular and cellular targets of ATP10C,Atp10cexpression was alteredin vitroin C2C12 skeletal muscle myotubes by transient transfection with anAtp10c-specific siRNA. Glucose uptake assays revealed that insulin stimulation caused a significant 2.54-fold decrease in 2-deoxyglucose uptake in transfected cells coupled with a significant upregulation of native mitogen-activated protein kinases (MAPKs), p38, and p44/42. Additionally, glucose transporter-1 (GLUT1) was significantly upregulated; no changes in glucose transporter-4 (GLUT4) expression were observed. The involvement of MAPKs was confirmed using the specific inhibitor SB203580, which downregulated the expression of native and phosphorylated MAPK proteins in transfected cells without any changes in insulin-stimulated glucose uptake. Results indicate thatAtp10cregulates glucose metabolism, at least in part via the MAPK pathway, and, thus, plays a significant role in the development of insulin resistance and type 2 diabetes.

scholarly journals Sorbitol increases muscle glucose uptake ex vivo and inhibits intestinal glucose absorption ex vivo and in normal and type 2 diabetic rats

2017 ◽  
Vol 42 (4) ◽  
pp. 377-383 ◽  
Author(s):  
Chika Ifeanyi Chukwuma ◽  
Md. Shahidul Islam
Keyword(s):  
Glycemic Control ◽  
Glucose Uptake ◽  
Ex Vivo ◽  
Glucose Absorption ◽  
Diabetic Rats ◽  
Dependent Manner ◽  
Intestinal Glucose Absorption ◽  
Type 2 Diabetic ◽  
Isolated Rat

Previous studies have suggested that sorbitol, a known polyol sweetener, possesses glycemic control potentials. However, the effect of sorbitol on intestinal glucose absorption and muscle glucose uptake still remains elusive. The present study investigated the effects of sorbitol on intestinal glucose absorption and muscle glucose uptake as possible anti-hyperglycemic or glycemic control potentials using ex vivo and in vivo experimental models. Sorbitol (2.5% to 20%) inhibited glucose absorption in isolated rat jejuna (IC50= 14.6% ± 4.6%) and increased glucose uptake in isolated rat psoas muscle with (GU50= 3.5% ± 1.6%) or without insulin (GU50= 7.0% ± 0.5%) in a concentration-dependent manner. Furthermore, sorbitol significantly delayed gastric emptying, accelerated digesta transit, inhibited intestinal glucose absorption, and reduced blood glucose increase in both normoglycemic and type 2 diabetic rats after 1 h of coingestion with glucose. Data of this study suggest that sorbitol exhibited anti-hyperglycemic potentials, possibly via increasing muscle glucose uptake ex vivo and reducing intestinal glucose absorption in normal and type 2 diabetic rats. Hence, sorbitol may be further investigated as a possible anti-hyperglycemic sweetener.

scholarly journals Meteorin-like (Metrnl) adipomyokine improves glucose tolerance in type 2 diabetes via AMPK pathway

2018 ◽  
Author(s):  
Jung Ok Lee ◽  
Hye Jeong Lee ◽  
Yong Woo Lee ◽  
Jeong Ah Han ◽  
Min Ju Kang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Underlying Mechanism ◽  
Dependent Manner ◽  
Beneficial Effects ◽  
Ampk Pathway

AbstractMeteorin-like (metrnl) is a recently identified adipomyokine that has beneficial effects on glucose metabolism. However, its underlying mechanism of action is not completely understood. In this study, we have shown that a level of metrnl increase in vitro under electrical-pulse-stimulation (EPS) and in vivo in exercise mice, suggesting that metrnl is an exercise-induced myokine. In addition, metrnl increases glucose uptake through the calcium-dependent AMPK pathway. Metrnl also increases the phosphorylation of HDAC5, a transcriptional repressor of GLUT4, in an AMPK-dependent manner. Phosphorylated HDAC5 interacts with 14-3-3 proteins and sequesters them in the cytoplasm, resulting in the activation of GLUT4 transcription. The intraperitoneal injection of recombinant metrnl improves glucose tolerance in mice with high fat-induced obesity or type 2 diabetes (db/db), but this is not seen in AMPK β1β2 muscle-specific null mice (AMPK β1β2 MKO). In conclusion, we have demonstrated that metrnl induces beneficial effects on glucose metabolism via AMPK and is a promising therapeutic candidate for glucose-related diseases such as type 2 diabetes.

Boerhaavia diffusa inhibits key enzymes linked to type 2 diabetes in vitro and in silico; and modulates abdominal glucose absorption and muscle glucose uptake ex vivo

2018 ◽  
Vol 106 ◽  
pp. 1116-1125 ◽  
Author(s):  
Olajumoke A. Oyebode ◽  
Ochuko L. Erukainure ◽  
Chika I. Chukwuma ◽  
Collins U. Ibeji ◽  
Neil A. Koorbanally ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Uptake ◽  
In Silico ◽  
Ex Vivo ◽  
Glucose Absorption ◽  
Key Enzymes ◽  
Boerhaavia Diffusa

scholarly journals Azadirachta indica inhibits key enzyme linked to type 2 diabetes in vitro, abates oxidative hepatic injury and enhances muscle glucose uptake ex vivo

2019 ◽  
Vol 109 ◽  
pp. 734-743 ◽  
Author(s):  
Olakunle Sanni ◽  
Ochuko L. Erukainure ◽  
Chika I. Chukwuma ◽  
Neil A. Koorbanally ◽  
Collins U. Ibeji ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Uptake ◽  
Azadirachta Indica ◽  
Hepatic Injury ◽  
Ex Vivo ◽  
Key Enzyme

scholarly journals Transthyretin and Amyloid in the Islets of Langerhans in Type-2 Diabetes

2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Gunilla T. Westermark ◽  
Per Westermark
Keyword(s):  
Type 2 Diabetes ◽  
Islets Of Langerhans ◽  
Islet Cells ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Amyloid Fibril Protein ◽  
Type 2 Diabetic

Transthyretin (TTR) is a major amyloid fibril protein in certain systemic forms of amyloidosis. It is a plasma protein, mainly synthesized by the liver but expression occurs also at certain minor locations, including the endocrine cells in the islets of Langerhans. With the use of immunohistochemistry and in situ hybridization, we have studied the distribution of transthyretin-containing cells in islets of Langerhans in type-2 diabetic and nondiabetic individuals. TTR expression was particularly seen in alpha (glucagon) cells. Islets from type-2 diabetic patients had proportionally more transthyretin-reactive islet cells, including beta cells. A weak transthyretin immunoreaction in IAPP-derived amyloid occurred in some specimens. In seeding experiments in vitro, we found that TTR fibrils did not seed IAPP while IAPP fibrils seeded TTR. It is suggested that islet expression of transthyretin may be altered in type-2 diabetes.

scholarly journals Effects of raising muscle glycogen synthesis rate on skeletal muscle ATP turnover rate in type 2 diabetes

2011 ◽  
Vol 301 (6) ◽  
pp. E1155-E1162 ◽  
Author(s):  
Ee L. Lim ◽  
Kieren G. Hollingsworth ◽  
Fiona E. Smith ◽  
Peter E. Thelwall ◽  
Roy Taylor
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Glycogen ◽  
Glycogen Synthesis ◽  
Turnover Rates ◽  
Atp Turnover ◽  
Muscle Glycogen Synthesis ◽  
Type 2 Diabetic

Mitochondrial dysfunction has been implicated in the pathogenesis of type 2 diabetes. We hypothesized that any impairment in insulin-stimulated muscle ATP production could merely reflect the lower rates of muscle glucose uptake and glycogen synthesis, rather than cause it. If this is correct, muscle ATP turnover rates in type 2 diabetes could be increased if glycogen synthesis rates were normalized by the mass-action effect of hyperglycemia. Isoglycemic- and hyperglycemic-hyperinsulinemic clamps were performed on type 2 diabetic subjects and matched controls, with muscle ATP turnover and glycogen synthesis rates measured using 31P- and 13C-magnetic resonance spectroscopy, respectively. In diabetic subjects, hyperglycemia increased muscle glycogen synthesis rates to the level observed in controls at isoglycemia [from 19 ± 9 to 41 ± 12 μmol·l−1·min−1 ( P = 0.012) vs. 40 ± 7 μmol·l−1·min−1 in controls]. This was accompanied by a modest increase in muscle ATP turnover rates (7.1 ± 0.5 vs. 8.6 ± 0.7 μmol·l−1·min−1, P = 0.04). In controls, hyperglycemia brought about a 2.5-fold increase in glycogen synthesis rates (100 ± 24 vs. 40 ± 7 μmol·l−1·min−1, P = 0.028) and a 23% increase in ATP turnover rates (8.1 ± 0.9 vs. 10.0 ± 0.9 μmol·l−1·min−1, P = 0.025) from basal state. Muscle ATP turnover rates correlated positively with glycogen synthesis rates ( rs = 0.46, P = 0.005). Changing the rate of muscle glucose metabolism in type 2 diabetic subjects alters demand for ATP synthesis at rest. In type 2 diabetes, skeletal muscle ATP turnover rates reflect the rate of glucose uptake and glycogen synthesis, rather than any primary mitochondrial defect.

Sign in / Sign up

Export Citation Format

Share Document