Abstract
BackgroundHuman data supporting a role for endoplasmic reticulum (ER) stress and calcium dyshomeostasis in diabetes is scarce. Darier disease (DD) is a hereditary skin disease caused by mutations in the ATP2A2 gene encoding the sarcoendoplasmic-reticulum ATPase 2 (SERCA2) calcium pump, which causes calcium dyshomeostasis and ER stress. We hypothesize that DD patients have a diabetes-like metabolic phenotype and the objective of this study was to examine the association between DD with impaired glucose tolerance and diabetes.MethodsCross-sectional clinical study on 25 DD patients and 25 matched controls. Metabolic status was assessed primarily by fasting blood glucose, oral glucose tolerance test, HOMA2-%S (insulin resistence) and HOMA2-%B (beta cell function).ResultsDD subjects showed normal oral glucose tolerance test and HOMA2-%S, while fasting blood glucose was lower and c-peptide as well as HOMA2-%B was higher.ConclusionIncreased HOMA2-%B values are indicative of increased basal insulin secretion which is a type of beta cell dysfunction associated to diabetes development. These results supports a role of ER stress in diabetes pathophysiology and contribute to the understanding of DD as a multi-organ syndrome.
Highlights
Human data supporting a role for endoplasmic reticulum (ER) stress and calcium dyshomeostasis in diabetes is scarce
ER stress has been implicated in the pathophysiology of various diseases including diabetes, where it is involved in beta cell dysfunction [2]
To assess the potential effects of oral acitretin treatment on glucose homeostasis due to the possibility of low drug levels remaining as well as mutations, Darier disease (DD) patients were sub-grouped into acitretin treated vs. not acitretin and pathogenic vs. benign mutations; no significant differences were observed (Table 2)
Summary
Human data supporting a role for endoplasmic reticulum (ER) stress and calcium dyshomeostasis in diabetes is scarce. Darier disease (DD) is a hereditary skin disease caused by mutations in the ATP2A2 gene encoding the sarcoendoplasmic-reticulum ATPase 2 (SERCA2) calcium pump, which causes calcium dyshomeostasis and ER stress. Endoplasmic reticulum (ER) stress is a condition where an insult disrupts ER homeostasis and leads to accumulation of misfolded and unfolded proteins, which may lead to cellular dysfunction and even apoptosis [1]. ER stress has been implicated in the pathophysiology of various diseases including diabetes, where it is involved in beta cell dysfunction [2]. While there are plenty of animal studies, few if any, human studies have examined if primary ER stress conditions are associated
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