A Review of Mouse Models of Monogenic Diabetes and ER Stress Signaling.

  title={A Review of Mouse Models of Monogenic Diabetes and ER Stress Signaling.},
  author={Paraskevi Salpea and Cristina Cosentino and Mariana Igoillo-Esteve},
  journal={Methods in molecular biology},
Diabetes is a major public health problem: it is estimated that 420 million people are affected globally. Monogenic forms of diabetes are less common, but variants in monogenic diabetes genes have been shown to contribute to type 2 diabetes risk. In vitro and in vivo models of monogenic forms of diabetes related to the endoplasmic reticulum (ER) stress response provided compelling evidence on the role of ER stress and dysregulated ER stress signaling on β cell demise in type 1 and type 2… 
Insulin secretion deficits in a Prader-Willi syndrome β-cell model are associated with a concerted downregulation of multiple endoplasmic reticulum chaperones
Findings implicate PWS-imprinted genes in concerted regulation of ER chaperone biosynthesis and β-cell secretory pathway function, illuminating the pathophysiological basis of hormone deficits in PWS.


Targeted disruption of the Chop gene delays endoplasmic reticulum stress-mediated diabetes.
It is concluded that ER overload in beta cells causes ER stress and leads to apoptosis via Chop induction and a new therapeutic approach for preventing the onset of diabetes by inhibiting Chop induction or by increasing chaperone capacity in the ER is suggested.
Clinical implications of a molecular genetic classification of monogenic β-cell diabetes
It is proposed that the old clinical classifications of maturity-onset diabetes of the young and neonatal diabetes are obsolete and that specific genetic etiologies should be sought in four broad clinical situations because of their specific treatment implications.
Pancreatic beta-cell failure and diabetes in mice with a deletion mutation of the endoplasmic reticulum molecular chaperone gene P58IPK.
In vivo evidence is provided to support the concept that P58(IPK) functions as a signal for the downregulation of ER-associated proteins involved in the initial ER stress response, thus preventing excessive cell loss by degradation pathways.
Considerations and guidelines for mouse metabolic phenotyping in diabetes research
The most commonly used experimental tests to assess glucose and energy homeostasis in mice are described and some guidelines regarding the design, analysis and interpretation of these tests are provided, as well as for studies using genetic models.
Hyperglucagonemia in an animal model of insulin- deficient diabetes: what therapy can improve it?
Loss of insulin-mediated intra-islet suppression of glucagon production may be a contributor to hyperglycemia in Akita mice, and leptin treatment appears beneficial in such a circumstance.
Guanabenz Sensitizes Pancreatic &bgr; Cells to Lipotoxic Endoplasmic Reticulum Stress and Apoptosis
Guanabenz does not protect β cells from ER stress; instead, it potentiates lipotoxic ER stress through PERK/eIF2 α/CHOP signaling, demonstrating the crucial importance of the tight regulation of eIF2α phosphorylation for the normal function and survival of pancreatic β cells.
PERK (EIF2AK3) Regulates Proinsulin Trafficking and Quality Control in the Secretory Pathway
It is speculated that PERK acts as a metabolic sensor in the insulin-secreting β-cells to modulate the trafficking and quality control of proinsulin in the ER relative to the physiological demands for circulating insulin.
Endoplasmic reticulum stress, obesity and diabetes.