Study On The Insulin Resistance Of Pancreatic Beta Cell In Type 2 Diabetes Mellitus

Objectives To investigate whether there is an insulin resistance of pancreatic beta cell in the development of type 2 diabetes mellitus and it's possible roles in the pathogenesis of type 2 diabetes mellitus.Methods Firstly, in order to eliminate the paracrine effects of the glucagon and somatostatin on beta cells, the intact pancreatic islets of mice were co-incubated with anti-glucagon serum and anti-somatostatin serum. Then, the intact islets were cultured in a "stage-successive" way. The secretion of pancreatic beta cells was expressed in connecting peptide. The changes of connecting peptides were observed during the culture with and without exogenous insulin. Based on the effects of insulin in normal control mice, the biological effects of insulin on secretion of beta cells were established. The effects of insulin in spontaneous diabetic mice were compared with the control group. From the changes of the effects of insulin between the two strains of mice, we can postulate whether there is an insulin resistance of pancreatic beta cells in the spontaneous diabetic animal models.Results The free glucagon and somatostatin in the samples pretreated with anti-glucagon serum and anti-somatostatin serum were significantly decreased by more than 90%, compared with their normal controls, whichwere pretreated with normal serum. The connecting peptides secreted by pancreatic islets in normal control mice were significantly increased during the culture with insulin, while those in diabetic mice were a little complicated, some were unchanged, some were significantly increased.Conclusions 1) After pretreatment with anti-glucagon serum and anti-somatostatin serum, free glucagon and somatostatin in pancreatic islets were significantly decreased by more than 90%, so we reasonably think that the paracrine effects of glucagon and somatostatin on beta cells were inhibited effectively. 2) As the biological model, the pancreatic islets of BALB/c mice secreted more connecting peptides under the stimulation of lOOnM insulin. It indicates that there is a stimulatory effect of insulin on the secretion of beta cells in biological state. 3) As the pathological model, the pancreatic islets of KKAy mice varied in secretion of connecting peptides under the stimulation of lOOnM insulin. Sometime, they demonstrated no increase. Sometime, they demonstrated a significant increase. It indicates that there is no/a little stimulatory effect of insulin on the secretion of beta cells in pathological state. 4) Compared with BALB/c mice, KKAy mice showed a significant decrease in stimulatory effect of insulin on the secretion of pancreatic beta cells. 5) Considered the definition of insulin resistance, we concluded that, probably, there is an insulin resistance of pancreatic beta cells in spontaneous diabetic animals.