Non-insulin-dependent diabetes mellitus (NIDDM) occurs predominantly after the age of 50 years but is not easy to distinguish from late onset insulin-dependent diabetes. It is likely that misclassification is rare in a Caucasian population. Whilst NIDDM is widely believed to be genetically determined, recent epidemiological observations have consistently revealed statistical associations between indices of poor fetal and infant growth with susceptibility to loss of glucose tolerance in adult life.
The epidemiological links observed between fetal and infant growth and impaired glucose tolerance in adult life that led to the formulation of the "thrifty phenotype" hypothesis have been confirmed by others in widely differing populations. The proposed nutritional basis of these links has been tested in an animal model in which rat dams were fed an isocaloric low-protein diet and the postweaning normally fed offspring were studied.
Diabetes mellitus has evolved as a complication because of increased longevity of patients with cystic fibrosis (CF). CF-related diabetes (CFRD) is associated with increased morbidity and mortality, therefore, prompt diagnosis and aggressive management are important. The prevalence of CFRD increases with age with an age-dependent incidence rate of 5% per year; at 30 years 50% of patients are diabetic. CFRD develops insidiously.
Rapamycin, an inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, extends the life span of yeast, worms, flies, and mice. Interventions that promote longevity are often correlated with increased insulin sensitivity, and it therefore is surprising that chronic rapamycin treatment of mice, rats, and humans is associated with insulin resistance (J Am Soc Nephrol., 19, 2008, 1411; Diabetes, 00, 2010, 00; Science, 335, 2012, 1638).
Adiponectin secreted from adipocytes binds to adiponectin receptors AdipoR1 and AdipoR2, and exerts antidiabetic effects via activation of AMPK and PPAR-? pathways, respectively. Levels of adiponectin in plasma are reduced in obesity, which causes insulin resistance and type 2 diabetes. Thus, orally active small molecules that bind to and activate AdipoR1 and AdipoR2 could ameliorate obesity-related diseases such as type 2 diabetes. Here we report the identification of orally active synthetic small-molecule AdipoR agonists.
In Ayurvedic medicine, Salacia reticulata is known to be useful against various metabolic diseases, including diabetes and obesity. In this study, we attempted to clarify the antiobesity mechanism and the safety of S. reticulata in vivo and in vitro. We gave ordinary MF feed, alone or mixed with S. reticulata (0.3 or 1.0%), to Tsumura Suzuki obesity diabetes (TSOD) mice (spontaneous obese type II diabetes model mice) and Tsumura Suzuki non-obese (TSNO) mice (the corresponding reference animals), ad libitum for 2 months.
Experimentally-induced hyperglycemia by prolonged glucose infusion allows investigation of the effects of sustained stimulation of the pancreatic beta-cell on insulin secretion and sensitivity. Hormonal responses to a meal following prolonged glucose infusions have not been investigated. To determine if a 48-h glucose infusion alters hormonal responses to a test meal as well as food intake and hunger in normal weight individuals, 16 subjects (8 men, 8 women, age 18-30 years, mean BMI=21.7+/-1.6 kg/m2) were infused for 48 h with either saline (50 ml/h) or 15% glucose (200 mg/m2/min).
American Journal of Physiology. Endocrinology and Metabolism
Berberine, a botanical alkaloid used to control blood glucose in type 2 diabetes in China, has recently been reported to activate AMPK. However, it is not clear how AMPK is activated by berberine. In this study, activity and action mechanism of berberine were investigated in vivo and in vitro. In dietary obese rats, berberine increased insulin sensitivity after 5-wk administration. Fasting insulin and HOMA-IR were decreased by 46 and 48%, respectively, in the rats.
American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
The prevalence of type 2 diabetes (T2DM) is increasing, creating a need for T2DM animal models for the study of disease pathogenesis, prevention, and treatment. The purpose of this project was to develop a rat model of T2DM that more closely models the pathophysiology of T2DM in humans. The model was created by crossing obese Sprague-Dawley rats with insulin resistance resulting from polygenic adult-onset obesity with Zucker diabetic fatty-lean rats that have a defect in pancreatic beta-cell function but normal leptin signaling.
