Narrow-leafed lupin (Lupinus angustifolius L.) seed β-conglutins reverse the induced insulin resistance in pancreatic cells

Food Funct. 2018 Oct 17;9(10):5176-5188. doi: 10.1039/c8fo01164h.

Abstract

Insulin resistance (IR) is the main contributor to the development of type 2 diabetes. In this study, we have purified recombinant β-conglutin proteins (rβ1 to rβ4, and rβ6) from narrow-leafed lupin (NLL) by using affinity chromatography. The objective of this study was to evaluate the capacity of these β-conglutins to improve the IR state using ex vivo and in vitro systems. rβ1, rβ3, and rβ6 produced lower levels of pro-inflammatory mediator nitric oxide (about -7-fold in all cases), up-regulated mRNA expression levels of IRS-1 (+201, +173, +192%) and Glut-4 (+286, +121, +147%), increased levels of p85-PI3K (+188, +187, +137-fold) and Glut-4 (+503, +548, +515-fold) proteins, higher phosphorylation levels of the insulin signalling pathway activator p-IRS-1 and downstream mediators such as p-Akt, p-Cbl, and p-caveolin, and improved glucose uptake in insulin resistant (IR-C) culture cells. β-conglutin proteins were able to suppress the oxidative stress produced by insulin-induced resistance on PANC-1 control (C) cells by strongly reducing the protein oxidative carbonylation induced by ROS and balancing the metabolic homeostasis in IR-C cells through regulation of mRNA expression. At the same time, β-conglutins are able to reduce the levels of the pro-inflammatory mediator nitric oxide and promote the anti-oxidative capacity of cells by increasing the levels of reduced glutathione. These results suggest NLL β-conglutins might play a fundamental role as functional food components, since β-conglutins' nutraceutical properties could enhance the effectiveness of dietary improvement of type 2 diabetes complications.

MeSH terms

  • Adult
  • Cell Line
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism
  • Humans
  • Insulin / metabolism*
  • Insulin Receptor Substrate Proteins / genetics
  • Insulin Receptor Substrate Proteins / metabolism
  • Insulin Resistance*
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism*
  • Lupinus / chemistry*
  • Male
  • Middle Aged
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Plant Extracts / administration & dosage*
  • Plant Extracts / isolation & purification
  • Seed Storage Proteins / administration & dosage*
  • Seed Storage Proteins / isolation & purification
  • Seeds / chemistry

Substances

  • Glucose Transporter Type 4
  • IRS1 protein, human
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Plant Extracts
  • Seed Storage Proteins
  • conglutin protein, Lupinus angustifolius