Abstract
Acacia arabica is used traditionally to treat a variety of ailments, including diabetes. This study elucidated the antidiabetic actions of A. arabica bark together with the isolation of bioactive molecules. Insulin secretion and signal transduction were measured using clonal β cells and mouse islets. Glucose uptake was assessed using 3T3-L1 adipocytes, and in vitro systems assessed additional glucose-lowering actions. High-fat-fed (HFF) obese rats were used for in vivo evaluation, and phytoconstituents were isolated and characterised by RP-HPLC followed by LC-MS and NMR. Hot-water extract of A. arabica (HWAA) increased insulin release from clonal β cells and mouse islets by 1.3–6.8-fold and 1.6–3.2-fold, respectively. Diazoxide, verapamil and calcium-free conditions decreased insulin-secretory activity by 30–42%. In contrast, isobutylmethylxanthine (IBMX), tolbutamide and 30 mM KCl potentiated the insulin-secretory effects. The mechanism of actions of HWAA involved membrane depolarisation and elevation of intracellular Ca2+ together with an increase in glucose uptake by 3T3-L1 adipocytes, inhibition of starch digestion, glucose diffusion, dipeptidyl peptidase-IV (DPP-IV) enzyme activity and protein glycation. Acute HWAA administration (250 mg/5 mL/kg) enhanced glucose tolerance and plasma insulin in HFF obese rats. Administration of HWAA (250 mg/5 mL/kg) for 9 days improved glucose homeostasis and β-cell functions, thereby improving glycaemic control, and circulating insulin. Isolated phytoconstituents, including quercetin and kaempferol, increased insulin secretion in vitro and improved glucose tolerance. The results indicate that HWAA has the potential to treat type 2 diabetes as a dietary supplement or as a source of antidiabetic agents, including quercetin and kaempferol.
Highlights
Diabetes mellitus (DM) is one of the fastest-growing metabolic disorders resulting from deficiency of insulin, disturbed beta-cell function or insulin resistance [1]
Type 2 diabetes mellitus (T2DM) is commonly found over the age of 40, but it is increasingly common in children and young adults due to childhood obesity, which causes beta-cell dysfunction and insulin resistance
The basal rate of insulin release from BRIN-BD11 cells in the presence of 5.6 mM glucose was 0.87 ± 0.03 ng/106 cells/20 min, and this rate increased to 4.45 ± 0.53 ng/106 cells/20 min (p < 0.05; n = 8) in the presence of alanine (10 mM) (Figure 1A)
Summary
Diabetes mellitus (DM) is one of the fastest-growing metabolic disorders resulting from deficiency of insulin, disturbed beta-cell function or insulin resistance [1]. Type 2 diabetes mellitus (T2DM) is commonly found over the age of 40, but it is increasingly common in children and young adults due to childhood obesity, which causes beta-cell dysfunction and insulin resistance. Both major forms of diabetes are characterised by hyperglycaemia, which is a major player in the risk of developing diabetic complications such as cardiovascular disease, neuropathy, retinopathy and nephropathy [2]. Weight loss and the use of single or multiple oral antidiabetic drugs are prevalent treatment options for T2DM Such agents, including DPP-IV inhibitors and glucagon-like peptide-1 mimetics, are being used to improve glucose tolerance via the potentiation of glucose-stimulated insulin secretion [2,3]. These options are often expensive and have secondary side effects that sometimes limit their use in wider and poorer sections of society
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