Expression Of Protein Tyrosine Phosphatase-1B And Islet Amyloid Peptide In Pancreas Of Diabetes And Pancreatic Cancer

Background and ObjectivesPancreatic cancer is a malignant tumer of digestive system with rapidly progress, very poor prognosis and high fatality rate, the incidence rate in recent years significantly increased. With the improvement of people's standard of living and changes of lifestyle and the structure of diet, the incidence of diabetes has increased year by year. Research shows that pancreatic cancer and diabetes is a close correlation. Epidemiological survey found that incidence rates of diabetes in pancreatic cancer patients was as high as 20% to 30%, and diabetes is also an independent risk factor of pancreatic cancer, studies indicated the relative risk of PC for diabetics to be 1.5～2 times than the general population, and that the course of diabetes and the risk of pancreatic cancer was positively correlated. But mechanisms of long-term diabetes causing pancreatic cancer, as well as its precise interaction of the two diseases is still not clear.Protein tyrosine phosphatase-1B (PTP-1B) is a member of protein tyrosine phosphatase family, and is an important control factor in the signal transduction pathway, regulating signal transduction through its phosphatase activity, thereby impact on cell growth, apoptosis, adhesion and migration, and have close relations with human diseases, especially diabetes and cancer.Existing research data shows that the changed expression of islet amyloid polypeptide (IAPP) is one of the important mechanisms of apoptosis of pancreaticβ-cells, animal experiment shows that islet amyloid deposition damaged isletβ-cells, resulting in impairedβ-cell function, and then induced impaired glucose tolerance in turn lead to diabetes, therefore, the islet amyloid deposition of animals can be a cause of impaired glucose tolerance and diabetes. And researches showed that, the concentration of plasma IAPP changed with related tumors. But there is no finding of IAPP in human pancreatic tissue.This study is divided into two parts: the first part for the expression of protein tyrosine phosphatase-1B(PTP-1B) in patients with diabetes mellitus and pancreatic cancer, the second part for the expression of islei amyloid polypeptide (IAPP) in patients with diabetes mellitus and pancreatic cancer, aimed at detecting the changes of IAPP and PTP1B in patients with type 2 diabetes and pancreatic cancer, and to explore whether such a change can be pathogenesis of both diabetes and pancreatic cancer.Methods1. Experimental groups: collection of surgical resection of pancreatic cancer and adjacent tumor-free region, along with a history of diabetes or not, operative specimens were classified as diabetic group, pancreatic cancer group and the control group, all surgical specimens were divided into four groups: A for pancreatic cancer + diabetes ,B for pancreatic tissue (tumor-free region) + diabetes ,C for pancreatic cancer + normal blood glucose,D for pancreatic tissue (tumor-free region) + normal blood glucose. 2. all specimens were identifid tissue types by HE staining; 3. using immunohistochemical methods to detect expression of PTP-1B and IAPP of the four groups, and the application of quantitative MIQAS medical image analysis system, the medical quantitative image analysis software for staining intensity; 4. Application of Western-blot method for the expression of PTP-1B and IAPP, using Quantity One software (Bio-Rad) scanning X-ray film and gray semi-quantitative analysis at the same time for statistical analysis.ResultsPartⅠ: 1. Immunohistochemical indicated that PTP-1B expressed in human pancreatic islet cell cytoplasm, four samples showed positive staining results, but different staining intensity, in the diabetic group (A + B) and pancreatic cancer group (A + C), expression was significantly higher (P<0.01), and between the various groups are statistically significant: (1) diabetic patients with pancreatic cancer (group A) were strongly positive staining, and compared with diabetes and adjacent pancreatic tissue group (group B) showed obvious statistical significance (P<0.01) (2) normal glucose and pancreatic cancer (group C) staining intensity higher than normal blood sugar adjacent pancreatic tissue group (group D), contrast has obvious statistical significance (P<0.01) (3) diabetic patients with pancreatic cancer (group A) were stronger than normal blood glucose and pancreatic cancer (group C) (P<0.01) (4) Diabetes adjacent pancreatic tissue group (B) stronger than normal blood sugar adjacent pancreatic tissue group (group D) (P<0.05).2. Western-blot method detecting protein content, the result, different groups of different protein content, expression of PTP-1B in diabetes group and pancreatic cancer group obviously increased, statistically significantly compared with the control group, get the same results as above-mentioned, the results of immunohistochemistry.PartⅡ: 1 .Immunohistochemical indicated that IAPP expressed in human pancreatic islet cell cytoplasm, four samples showed positive staining results, but different staining intensity, in the diabetic group (A + B) and pancreatic cancer group (A + C), expression was significantly higher (P<0.01), and between the various groups are statistically significant: (1) diabetic patients with pancreatic cancer (group A) were strongly positive staining, and compared with diabetes and adjacent pancreatic tissue group (group B) showed obvious statistical significance (P<0.01) (2) normal glucose and pancreatic cancer (group C) staining intensity higher than normal blood sugar adjacent pancreatic tissue group (group D), contrast has obvious statistical significance (P<0.01) (3) diabetic patients with pancreatic cancer (group A) were stronger than normal blood glucose and pancreatic cancer (group C) (P<0.01) (4) Diabetes adjacent pancreatic tissue (group B) stronger than normal blood sugar adjacent pancreatic tissue group (group D) ,but not statistical significantly (P>0.05).2. Western-blot method detecting protein content, the result, different groups of different protein content, expression of IAPP in diabetes group and pancreatic cancer group obviously increased, statistically significantly compared with the control group, the first three comparion of the groups were same with the above, but the comparion between group B and group D is still statistical significant (P<0.05), and was not exactly the same results with immunohistochemistry.ConclusionsExpression of PTP-1B and IAPP both increased significantly in pancreatic tissue with diabetes and in pancreatic cancer tissue, indicating that they participated in the course of diabetes and pancreatic cancer, and may be the common pathogenesis of the disease.