title: ER stress in rodent islets of Langerhans is concomitant with obesity and β-cell compensation but not with β-cell dysfunction and diabetes.
abstract: OBJECTIVE
  The objective of this study was to determine whether ER stress correlates with β-cell dysfunction in obesity-associated diabetes.
  
  
  METHODS
  Quantitative RT-PCR and western blot analysis were used to investigate changes in the expression of markers of ER stress, the unfolded protein response (UPR) and β-cell function in islets isolated from (1) non-diabetic Zucker obese (ZO) and obese female Zucker diabetic fatty (fZDF) rats compared with their lean littermates and from (2) high-fat-diet-fed fZDF rats (HF-fZDF), to induce diabetes, compared with age-matched non-diabetic obese fZDF rats.
  
  
  RESULTS
  Markers of an adaptive ER stress/UPR and β-cell function are elevated in islets isolated from ZO and fZDF rats compared with their lean littermates. In islets isolated from HF-fZDF rats, there was no significant change in the expression of markers of ER stress compared with age matched, obese, non-diabetic fZDF rats.
  
  
  CONCLUSIONS
  These results provide evidence that obesity-induced activation of the UPR is an adaptive response for increasing the ER folding capacity to meet the increased demand for insulin. As ER stress is not exacerbated in high-fat-diet-induced diabetes, we suggest that failure of the islet to mount an effective adaptive UPR in response to an additional increase in insulin demand, rather than chronic ER stress, may ultimately lead to β-cell failure and hence diabetes.
authors.affiliation: Department of Cell Physiology and Pharmacology, The Henry Wellcome Building, University of Leicester, University Road, Leicester, UK.
authors.forename: O
authors.initials: O
authors.lastname: Omikorede
authors.forename: C
authors.initials: C
authors.lastname: Qi
authors.forename: T
authors.initials: T
authors.lastname: Gorman
authors.forename: P
authors.initials: P
authors.lastname: Chapman
authors.forename: A
authors.initials: A
authors.lastname: Yu
authors.forename: D M
authors.initials: DM
authors.lastname: Smith
authors.forename: T P
authors.initials: TP
authors.lastname: Herbert