Lupin seed hydrolysate promotes G-protein-coupled receptor, intracellular Ca2+ and enhanced glycolytic metabolism-mediated insulin secretion from BRIN-BD11 pancreatic beta cells

Mrunmai Tapadia; Rodrigo Carlessi; Stuart Johnson; Ranjeet Utikar; Philip Newsholme

doi:10.1016/j.mce.2018.10.015

Lupin seed hydrolysate promotes G-protein-coupled receptor, intracellular Ca²⁺ and enhanced glycolytic metabolism-mediated insulin secretion from BRIN-BD11 pancreatic beta cells

Mol Cell Endocrinol. 2019 Jan 15:480:83-96. doi: 10.1016/j.mce.2018.10.015. Epub 2018 Oct 19.

Authors

Mrunmai Tapadia¹, Rodrigo Carlessi², Stuart Johnson³, Ranjeet Utikar¹, Philip Newsholme⁴

Affiliations

¹ Western Australia School of Mines (WASM): Minerals, Energy and Chemical Engineering, Curtin University, Perth, WA, 6102, Australia.
² School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute Biosciences, Curtin University, Perth, WA, 6102, Australia. Electronic address: rodrigo.carlessi@curtin.edu.au.
³ School of Molecular and Life Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, 6845, Australia.
⁴ School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute Biosciences, Curtin University, Perth, WA, 6102, Australia. Electronic address: philip.newsholme@curtin.edu.au.

PMID: 30347229
DOI: 10.1016/j.mce.2018.10.015

Abstract

Lupin seed proteins have been reported to exhibit hypoglycaemic effects in animals and humans following oral administration, however little is known about its mechanism of action. This study investigated the signalling pathway(s) responsible for the insulinotropic effect of the hydrolysate obtained from lupin (Lupinus angustifolius L.) seed extracts utilizing BRIN-BD11 β-cells. The extract was treated with digestive enzymes to give a hydrolysate rich in biomolecules ≤7 kDa. Cells exhibited hydrolysate induced dose-dependent stimulation of insulin secretion and enhanced intracellular Ca²⁺ and glucose metabolism. The stimulatory effect of the hydrolysate was potentiated by depolarizing concentrations of KCl and was blocked by inhibitors of the ATP sensitive K⁺ channel, Gα_q protein, phospholipase C (PLC) and protein kinase C (PKC). These findings reveal a novel mechanism for lupin hydrolysate stimulated insulin secretion via Gα_q mediated signal transduction (Gα_q/PLC/PKC) in the β-cells. Thus, lupin hydrolysates may have potential for nutraceutical treatment in type 2 diabetes.

Keywords: Gα(q) protein; Hypoglycaemic; Insulinotropic; Lupin; Nutraceutical; β-Cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium / metabolism*
Cell Membrane / drug effects
Cell Membrane / metabolism
Cell Respiration / drug effects
Cell Survival / drug effects
Cyclic AMP / metabolism
Cyclic AMP-Dependent Protein Kinases / metabolism
Glucose / metabolism
Glycolysis* / drug effects
Hot Temperature
Humans
Hydrolysis
Insulin Secretion* / drug effects
Insulin-Secreting Cells / drug effects
Insulin-Secreting Cells / metabolism*
Intracellular Space / metabolism
Lupinus / chemistry*
Mitochondria / drug effects
Mitochondria / metabolism
Palmitic Acid / toxicity
Plant Extracts / pharmacology*
Receptors, G-Protein-Coupled / metabolism*
Seeds / chemistry*
Signal Transduction / drug effects
Type C Phospholipases / metabolism

Substances

Plant Extracts
Receptors, G-Protein-Coupled
Palmitic Acid
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
Type C Phospholipases
Glucose
Calcium