The beneficial effect of growth hormone treatment on islet mass in streptozotocin-treated mice.

BACKGROUND: Type 1 diabetes is an autoimmune disease, characterized by a loss of pancreatic ß-cell mass and function, which results in dramatic reductions in insulin secretion and circulating insulin levels. Patients with type 1 diabetes are traditionally treated with insulin injections and insulin pumps ex vivo or undergo transplantation. Growth hormone (GH) has been shown to be involved in ß-cell function and survival in culture. METHODS: Twelve-week-old female C57BL/6 mice were treated with streptozotocin and monitored for their weight and blood glucose levels. Fourteen days post-initial injection, these mice were separated into two groups at random. One group was treated with GH while the other treated with vehicle for up to 3 weeks. These mice were compared with mice not treated with streptozotocin. RESULTS: Under our experimental conditions, we observed that mice treated with GH had larger islets and higher serum insulin levels than streptozotocin-treated mice treated with saline (0.288 vs. 0.073 ng/mL, p < 0.01). CONCLUSIONS: Our data demonstrate that GH may rescue islets and therefore may possess therapeutic potential in the treatment of type 1 diabetes, although consideration should be made regarding GH's effect on insulin resistance.

The epidemiology and molecular mechanisms linking obesity, diabetes, and cancer.

The worldwide epidemic of obesity is associated with increasing rates of the metabolic syndrome and type 2 diabetes. Epidemiological studies have reported that these conditions are linked to increased rates of cancer incidence and mortality. Obesity, particularly abdominal obesity, is associated with insulin resistance and the development of dyslipidemia, hyperglycemia, and ultimately type 2 diabetes. Although many metabolic abnormalities occur with obesity and type 2 diabetes, insulin resistance and hyperinsulinemia appear to be central to these conditions and may contribute to dyslipidemia and altered levels of circulating estrogens and androgens. In this review, we will discuss the epidemiological and molecular links between obesity, type 2 diabetes, and cancer, and how hyperinsulinemia and dyslipidemia may contribute to cancer development. We will discuss how these metabolic abnormalities may interact with estrogen signaling in breast cancer growth. Finally, we will discuss the effects of type 2 diabetes medications on cancer risk.

Hyperinsulinemia increases placenta endothelin-converting enzyme-1 expression in trophoblasts.

BACKGROUND: Exogenous hyperisulinemia causes pregnancy, induced hypertension and intrauterine growth restriction (IUGR) in pregnant rats. Hyperinsulinemia may increase production of endothelin-1 (ET-1), produced by sequential proteolysis of the big endothelin by the endothelin-converting enzyme (ECE)-1, the expression of which is examined here in the placenta, kidney, heart, and liver. METHODS: Rats were rendered hyperinsulinemic by subcutaneous insulin pellet, mated and followed to the twenty-first day of pregnancy. They were then killed, and their fetuses and placentas were examined. RESULTS: Hyperinsulinemic dams (HD) had higher blood pressure (BP) (130 ± 17 mm Hg in HD vs. 115 ± 16 mm Hg in normal pregnant dams (NPD), P < 0.05), lower placenta weight (0.44 ± 0.08 g in HD vs. 0.47 ± 0.08 NPD, P < 0.05) and lower fetus weight: males 4.9 ± 0.4 g in HD vs. 5.5 ± 0.4 g in NPD, P < 0.0001; females 4.7 ± 0.4 g in HD vs. 5.2 ± 0.4 g in NPD (P < 0.0001). ECE-1 expression as determined by western blot was significantly increased in the placenta and its implantation site, i.e., the mesometrial triangle (MT) of HD by 46 and 48%, respectively. In the kidney and heart of HD ECE-1, protein expression was increased by 230 and 220%, respectively, but its level in the liver was similar in both groups. Immunohistochemical staining revealed ECE-1 expression in endothelial cells and trophoblastic cells of the placenta and MT. Endothelin receptor A (ET-A), a mediator of vasoconstriction by ET-1, was also expressed in the endothelium and in trophoblasts of the placenta and MT. The expression of both ECE-1 and ET-A, as measured by automated image analysis, was generally stronger in placentas of HD. CONCLUSIONS: ECE-1 and ET-A are expressed in the trophoblastic cells of the placenta and MT. This may affect local endothelin levels, BP and IUGR.