Nod1-mediated lipolysis promotes diacylglycerol accumulation and successive inflammation via PKCδ-IRAK axis in adipocytes.

Chronic inflammation contributes to obesity mediated metabolic disturbances, including insulin resistance. Obesity is associated with altered microbial load in metabolic tissues that can contribute to metabolic inflammation. Different bacterial components such as, LPS, peptidoglycans have been shown to underpin metabolic disturbances through interaction with host innate immune receptors.

Isoalantolactone derivative promotes glucose utilization in skeletal muscle cells and increases energy expenditure in db/db mice via activating AMPK-dependent signaling.

Augmenting glucose utilization and energy expenditure in skeletal muscle via AMP-activated protein kinase (AMPK) is an imperative mechanism for the management of type 2 diabetes. Chemical derivatives (2a-2h, 3, 4a-4d, 5) of the isoalantolactone (K007), a bioactive molecule from roots of Inula racemosa were synthesized to optimize the bioactivity profile to stimulate glucose utilization in skeletal muscle cells. Interestingly, 4a augmented glucose uptake, driven by enhanced translocation of glucose transporter 4 (GLUT4) to cell periphery in L6 rat skeletal muscle cells.

Glucose uptake stimulatory potential and antidiabetic activity of the Arnebin-1 from Arnabia nobelis.

The enhanced disposal of glucose by the peripheral tissue is an important mechanism to regulate hyperglycemia. Here, we investigated the effect of Arnebin-1 from Arnebia nobilis, on glucose disposal in skeletal muscle cells and explored its in vivo antihyperglycemic potential. In L6 myotubes, Arnebin-1 stimulated glucose uptake, mediated through the enhanced translocation of the glucose transporter-4 (GLUT4) to plasma membrane, without changing the amount of GLUT4 or GLUT1.

Deoxyandrographolide promotes glucose uptake through glucose transporter-4 translocation to plasma membrane in L6 myotubes and exerts antihyperglycemic effect in vivo.

Skeletal muscle is the principal site for postprandial glucose utilization and augmenting the rate of glucose utilization in this tissue may help to control hyperglycemia associated with diabetes mellitus. Here, we explored the effect of Deoxyandrographolide (DeoAn) isolated from the Andrographis paniculata Nees on glucose utilization in skeletal muscle and investigated its antihyperglycemic effect in vivo in streptozotocin-induced diabetic rats and genetically diabetic db/db mice. In L6 myotubes, DeoAn dose-dependently stimulated glucose uptake by enhancing the translocation of glucose transporter 4 (GLUT4) to cell surface, without affecting the total cellular GLUT4 and GLUT1 content.

NOD2 activation induces oxidative stress contributing to mitochondrial dysfunction and insulin resistance in skeletal muscle cells.

Nucleotide-binding oligomerization domain protein-2 (NOD2) activation in skeletal muscle cells has been associated with insulin resistance, but the underlying mechanisms are not yet clear. Here we demonstrate the implication of oxidative stress in the development of mitochondrial dysfunction and insulin resistance in response to NOD2 activation in skeletal muscle cells. Treatment with the selective NOD2 ligand muramyl dipeptide (MDP) increased mitochondrial reactive oxygen species (ROS) generation in L6 myotubes.

Fructose induces mitochondrial dysfunction and triggers apoptosis in skeletal muscle cells by provoking oxidative stress.

Mitochondrial dysfunction in skeletal muscle has been implicated in the development of insulin resistance, a major characteristic of type 2 diabetes. There is evidence that oxidative stress results from the increased production of reactive oxygen species and reactive nitrogen species leads to mitochondrial dysfunction, tissue damage, insulin resistance, and other complications observed in type 2 diabetes. It has been suggested that intake of high fructose contributes to insulin resistance and other metabolic disturbances.

Glycolipids: isolated from Oplismenus burmannii induce glucose uptake in L6-GLUT4myc myotube cells.

Bioactivity guided separation of combined n-hexane and chloroform extracts of Oplismenus burmannii resulted in the isolation and characterization of five new glycoglycerolipids, (2S)-1,2,6'-tri- O-hexadecanoyl-3-O-β-D-galactopyranosyl glycerol (1a), (2S)-1,2,6'-tri-O-[(9Z,12Z)-octadeca-9,12- dienoyl]-3-O-β-D-galactopyranosyl glycerol (1b), (2S)-1,6'-di-O-[(9Z,12Z)-octadeca-9,12-dienoyl]-3- O-β-D-galactopyranosyl glycerol (2b), (2S)-1,6'-di-O-[(9Z,12Z,15Z)-octadeca-9,12,15-trienoyl]-3-O-β-D-galactopyranosyl glycerol (2c), and (2S)-1,2-di-O-[(9Z,12Z)-octadeca-9,12-dienoyl]-3-O-(6- sulpho-α-D)-quinovopyranosyl glycerol (3b) along with five known glycoglycerolipids (1c, 2a, 3a, 3c and 4), a cerebroside (5), three monoacylglycerols (6a-c) and α-linoleic acid (7). The isolated compounds, 1-5 were in-vitro tested for their antihyperglycemic potential in terms of increase in 2-deoxyglucose uptake in L6-GLUT4myc myotube cells. The results showed that compounds, 1-5 were showing 1.

Design and synthesis of lupeol analogues and their glucose uptake stimulatory effect in L6 skeletal muscle cells.

Structure modifications of lupeol at the isopropylene moiety have been described via allylic oxidation using selenium dioxide. The antidiabetic efficacy of lupeol analogues were evaluated in vitro as glucose uptake stimulatory effect in L6 skeletal muscle cells. From all tested compounds, 2, 3, 4b and 6b showed significant stimulation of glucose uptake with respective percent stimulation of 173.