Estrogen increases glucose-induced insulin secretion from mouse pancreatic islets cultured in a prolonged high glucose condition.

BACKGROUND: It is known that males are more susceptible to develop type 2 diabetes than females. Estrogen has a protective effect on pancreatic islet against toxic agent such as amyloid. The role of estrogen in protection pancreatic islet against high glucose is still unknown. OBJECTIVE: Administration of estrogen in an ovariectomised animal shows a protective effect against type 2 diabetes. The present study aimed to determine the direct effect of estrogen on the islet function after prolonged culture in high glucose. MATERIAL AND METHOD: Estrogen (10-1 M in ethanol) was co-cultured with mouse pancreatic islets in normal glucose medium (11.1 mM) for 3 hours or with normal and high glucose medium (40 mM) for 10 days. RESULTS: Estrogen increased glucose-induced insulin secretion in islet culture in normal glucose medium for both 3-hour and 10-day culture. Prolonged exposure of pancreatic islet to high glucose generated impaired glucose-induced insulin secretion, which was partially abrogated by the presence of 10(-5) M estrogen. CONCLUSION: These results indicated a direct effect of estrogen on improving insulin secretion from mouse pancreatic islets that has been impaired by prolonged exposure to high glucose.

Estrogen reduced blood glucose in high fat-fed mice: An animal model of type 2 diabetes.

Objective: This study aims to produce a mouse model of type 2 diabetes by using high fat diet. The C57BL/6J mouse strain can develop type 2 diabetes by putting on high fat diet. Methods: A group of C57BL/6J male mice were fed with a high fat diet (53% energy by fat) while another group was fed with normal diet (4.5% energy by fat). Results: At the 16th week of feeding study, the high fat-fed mice developed type 2 diabetes and had higher fat-pad weight than the normal diet-fed mice. However, plasma triglyceride (TG) levels of the two groups were not different. High fat-induced diabetic mice were administered 0.2 ตg/g body weight of 17-β estradiol for 2 weeks. Their fasting blood levels were reduced to become lesser than the levels in high-fat fed mice without estrogen. A trend of decrease in plasma TG level of 17β estradiol treated mice was observed. Conclusion: This study demonstrated that high fat diet could induce type 2 diabetes in a mouse model and that estrogen could reduce the fasting blood glucose in these mice.

In vitro study of insulin secretion from mouse pancreatic islets-siriraj experiences.

Pancreatic islet isolation and culture technique are tools for direct investigation of the effects of substances on insulin secretion. Glucose is a well known insulin stimulating substance from the pancreatic islet. This study aims to demonstrate the first success (in Thailand) in islet isolation with intact insulin secretion from a mouse pancreas using collagenase P enzyme and histopaque separation. Isolated islets were cultured in RPMI 1640 for 24 hours before undergoing a glucose stimulation test. Glucose at five different concentrations (2.8, 5.6, 10, 15 and 20 mM glucose was higher than with 2.8mM basal glucose concentration. Insulin secretion increased about 1.7 to 3.5 fold from a basal level of 2.8 mM glucose without any difference in insulin content at any glucose concentrations used. To our knowledge, these data demonstrate the first success in mouse pancreatic islet isolation and culture in Thailand. This technique can be used as a tool for further investigation of the in vitro effects of substances such as plants or new drugs on insulin secretion.

Estrogen receptor-alpha mRNA in primary breast cancer: relationship to estrogen and progesterone receptor proteins and other prognostic factors.

The estrogen receptor (ER)-alpha protein and ER mRNA were measured in 314 primary breast cancer patients by enzyme immunoassay (EIA) and reverse-transcription polymerase chain reaction (RT-PCR) assay, respectively. The positivity of ER protein was 53% while of ER mRNA was 37.6%. A significant positive association between ER phenotype and ER mRNA was observed (r = 0.40, p < 0.0001) with a positive-negative agreement between them of 71.8%. The percentage of ER-negative, progesterone receptor (PR)-positive breast tumors was 1.9% by EIA and 7% by RT-PCR assay. This may indicate a difference in ER variants in these studied patients. The ER protein and ER mRNA status were inversely related to tumor size and p53 positivity. Also, ER protein was frequently positive in patients with a higher number of lymph node invasions, well to moderate nuclear differentiated tumor cells and negative c-erbB-2 status. The difference of the ER or ER mRNA status regarding ages, menopausal status, tumor stages and histological types was not shown. In the present study, ER mRNA did not demonstrate a closer relationship to prognostic indicators of breast cancer than ER protein. Before including the ER mRNA assessment in routine investigations of breast cancer, its relationship to prognostic factors and survival outcome should be further assessed with a higher number of patients and a longer follow-up time.

Expression of p53, c-erbB-2 and cathepsin D in relation to hormone receptors in primary breast cancer.

The immunohistochemical expression of p53, c-erbB-2, and cathepsin D oncogene proteins was examined in 494 primary breast carcinomas. This study aimed to investigate an association of expression of these three proteins with other variables known to be related to poor prognosis as well as with 5-year disease free survival (DFS). P53, c-erbB-2, and cathepsin D alone or in combination was negatively correlated with the presence of estrogen and progesterone receptors in breast cancer tissues. Alteration of these oncogenes rendering an expression of the proteins may affect the synthesis of steroid receptor proteins during the course of breast cancers. However, their significance as predictors of 5- year DFS was not achieved in this group of patients. Lymph node invasion was the only independent indicator for recurrent or metastatic breast carcinoma.