We have shown that deletion of the endoplasmic reticulum stress-induced chaperone p58ipk in the mouse results in a perturbation of glucose and lipid homeostasis. Neonatal mice are smaller than wild type litter mates and weights remain significantly lower throughout their lifespan. One of the factors in lower body weights is the lack of fat stores. Hyperglycemia occurs as mice reach full maturity at about 4 to 5 months of age, in males, but much later in females, at about 15 to 18 months of age.
The cause of the hyperglycemia appears to be related to hypoinsilumemia as the result of a decrease in the number of pancreatic beta cells. We can not rule out the possibility of a developmental defect in beta cells thus not enough mature beta cells are being generated to produce insulin. However, we have shown that there is an increase in apoptosis of beta cells suggesting there is increased beta cell death associated with the lack of p58ipk. Increased cell death may be the result of increased ER stress, ie., adequate numbers of beta cells are being generated but large numbers are being eliminated by apoptosis.
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