abscisic-acid and Insulin-Resistance

Abscisic acid is a phytohormone found in fruits and vegetables and is endogenously produced in mammals. In humans and mice, lanthionine synthetase C-like 2 (LANCL2) has been characterized as the natural receptor for ABA. Herein, we characterize the efficacy of a fig fruit extract of ABA in promoting glycemic control. This ABA-enriched extract, at 0.125 µg ABA/kg body weight, improves glucose tolerance, insulin sensitivity and fasting blood glucose in diet-induced obesity (DIO) and db/db mouse models. In addition to decreasing systemic inflammation and providing glycemic control without increasing insulin, ABA extract modulates the metabolic activity of muscle. ABA increases expression of important glycogen synthase, glucose, fatty acid and mitochondrial metabolism genes and increases direct measures of fatty acid oxidation, glucose oxidation and metabolic flexibility in soleus muscle cells from ABA-treated mice with DIO. Glycolytic and mitochondrial ATP production were increased in ABA-treated human myotubes. Further, ABA synergized with insulin to dramatically increase the rate of glycogen synthesis. The loss of LANCL2 in skeletal muscle abrogated the effect of ABA extract in the DIO model and increased fasting blood glucose levels. This data further supports the clinical development of ABA in the treatment of pre-diabetes, type 2 diabetes and metabolic syndrome.

Topics: Abscisic Acid; Animals; Blood Glucose; Diabetes Mellitus, Type 2; Disease Models, Animal; Ficus; Glucose; Humans; Inflammation; Insulin; Insulin Resistance; Membrane Proteins; Mice; Mice, Inbred NOD; Mitochondria; Muscle Cells; Muscle, Skeletal; Obesity; Phosphate-Binding Proteins; Plant Extracts

to evaluate the effects of abscisic acid (ABA), contained in dwarf peaches, on the regression of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) conditions.. sixty-five patients with IFG or IGT were randomized to take ABA or placebo for 3 months. We evaluated: fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbA. a significant reduction of HbA. abscisic acid can be effective in ameliorating glyco-metabolic compensation and in reducing inflammatory status in patients with IFG or IGT.

Topics: Abscisic Acid; Aged; Alanine Transaminase; Aspartate Aminotransferases; Blood Glucose; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Dietary Supplements; Double-Blind Method; Fasting; Female; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Postprandial Period; Prediabetic State; Randomized Controlled Trials as Topic

Abscisic acid (ABA) is a natural phytohormone and peroxisome proliferator-activated receptor gamma (PPARgamma) agonist that significantly improves insulin sensitivity in db/db mice. Although it has become clear that obesity is associated with macrophage infiltration into white adipose tissue (WAT), the phenotype of adipose tissue macrophages (ATMs) and the mechanisms by which insulin-sensitizing compounds modulate their infiltration remain unknown. We used a loss-of-function approach to investigate whether ABA ameliorates insulin resistance through a mechanism dependent on immune cell PPARgamma. We characterized two phenotypically distinct ATM subsets in db/db mice based on their surface expression of F4/80. F4/80(hi) ATMs were more abundant and expressed greater concentrations of chemokine receptor (CCR) 2 and CCR5 when compared to F4/80(lo) ATMs. ABA significantly decreased CCR2(+) F4/80(hi) infiltration into WAT and suppressed monocyte chemoattractant protein-1 (MCP-1) expression in WAT and plasma. Furthermore, the deficiency of PPARgamma in immune cells, including macrophages, impaired the ability of ABA to suppress the infiltration of F4/80(hi) ATMs into WAT, to repress WAT MCP-1 expression and to improve glucose tolerance. We provide molecular evidence in vivo demonstrating that ABA improves insulin sensitivity and obesity-related inflammation by inhibiting MCP-1 expression and F4/80(hi) ATM infiltration through a PPARgamma-dependent mechanism.

Topics: Abscisic Acid; Adipose Tissue, White; Animals; Blood Glucose; Body Weight; Chemokine CCL2; Inflammation; Insulin Resistance; Liver; Macrophages; Mice; Mice, Inbred Strains; Obesity; Phenotype; PPAR gamma; Triglycerides