Noninvasive Imaging of Pancreatic Beta Cell Mass

There is currently no available method to non-invasively quantify the mass of insulin producing pancreatic beta cells. Beta cell mass is indirectly assessed by biochemical measurement of insulin secretion, usually after a form of glucose tolerance test. In this paper, Berrie Center investigators demonstrate that PET scanning with a compound called DTBZ can quantify beta cell mass in animals. Studies to extend these observations to humans are underway.

P. Harris et al. J. Clin. Invest. 2006.

Insulin and leptin are two hormones that decrease food intake by regulating key brain cells to produce appetite-inhibiting peptides and turn off the generation of appetite promoting peptides. In this study, we have provided a mechanism for the cooperating actions of these hormones by showing that they control the production of these appetite-regulating hormones via a common set of DNA-binding proteins, or transcription factors. These observations can hopefully be translated into more effective treatments for obesity.

T. Kitamura et al Nature Medicine 2006.

Diabetes is associated with increased incidence of atherosclerosis and its complications. It has been known for many years that the first step in the development of atherosclerosis in an increase in LDL-cholesterol production by the liver, but it's unclear how this may be related to diabetes. In this paper, we have identified a mechanism that links insulin resistance in the liver cell with excessive lipid production. In a follow-up paper, we have also shown that this results in increased atherosclerosis. These observations will hopefully lead to better approaches to combat atherosclerosis in diabetic patients.

M. Matsumoto, J. Clin. Invest. 2006.

Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. This paper describes the molecular physiology underlying the reductions in energy expenditure that occur with weight loss in human subjects. The work suggests that one cause for these responses  that act to cause weight regain  is a state of relative leptin deficiency.

M. Rosenbaum et al. J. Clin. Invest. 2005.

Monoclonal antibody antagonists of hypothalamic FGFR1 cause potent but reversible hypophagia and weight loss in rodents and monkeys. This paper demonstrates a role for the fibroblast growth factor receptor-1 (FGFR1) in the regulation of body weight (food intake) in two species. The receptor  in the hypothalamus - was manipulated using monoclonal antibodies to a specific spliceform of the receptor. This receptor gained access to the hypothalamus following systemic administration.

D. Haijun et al. Am J Physiol Endocrinol Metab, 2007.