NTU Undergraduates' research April 2014 - Biosciences | Seite 79

Hannah Birkett, N0376278

The Effect Of Glucolipotoxicity on the Pancreatic β-cell: With Focus on the Role of Small
GTPase Proteins, Rab4 and Rab7
Abstract
Type 2 Diabetes (T2D) is a fast-growing disorder with huge social, economic and health repercussions.
Glucolipotoxicity is a phenomenon referring to the combined effect of prolonged hyperglycaemia and
dyslipidaemia: accounting for the dysfunction and reduction in the mass of pancreatic β-cells.
Glucolipotoxicity is thought to be the main cause of Type 2 Diabetes: accounting for the induction of
apoptosis, low-grade inflammation and inhibition of glucose-stimulated insulin secretion(GSIS). Small
GTPase proteins, Rab4 and Rab7, are endosomal-trafficking proteins. Rab4 is localised to early
endosomes, responsible for the sorting, and recycling, of cell-surface receptors. Rab7 on the other-hand is
majorly involved in the degradation of these receptors through the late-endocytic pathway. The
expression of Rab4 and Rab7 were analysed in both control conditions and INS-1 cell extracts treated
with excess fatty acids and glucose. This paper reports that the induction of glucolipotoxic conditions
results in the upregulation of Rab4: fold-increase of 5.5±1.4. Rab7, on the other hand was downregulated.
The mechanisms underlying the increase seen in Rab4 were conclusively relative to the pathway of
mitogen-activated protein kinases(MAPK): inductive of β-cell apoptosis, inhibition of gene expression,
and and overall reduction of β-cell mass.
Keywords: Glucolipotoxicity, Islet β-cell, Endosomal Trafficking, Volatge-Gated Calcium Channels, MAPK’s, Rab4, Rab7.