Publications & Research
RESEARCH
Metabolic Disease
By employing methods that mimic the neurobiochemical physiology responsible for the seasonal shift from the obese, insulin resistant condition to the lean, insulin sensitive state common among vertebrate species in the wild, it is possible to develop new treatment strategies for human metabolic diseases such as type 2 diabetes, obesity, and metabolic syndrome. Changes in the circadian phase relations of distinct neuroendocrine rhythms drive the annual cycle of metabolism among vertebrates in the wild.
Consequently, it is not merely supplying the neuroendocrine factors of the “lean” season that produces leanness but rather supplying the circadian neuroendocrine blueprint that accomplishes this shift. Methods aimed at doing so, can function to alleviate and induce the obese, insulin resistant condition as is the case in the wild. We are developing different ways of applying this science to provide effective and practical means of treating human metabolic diseases.
Immune Disorders
Immuno-suppression and autoimmune diseases are both associated with derangements in the circadian neuroendocrine axis. Once again, it is the critical role of the brain-neuroendocrine axis to regulate and orchestrate the complex immunological interactions that occur at the cellular and tissue levels for the production of an organismal level immunocompetence.
Rather than focusing on specific immuno-modulators such chemokines or lymphkines to boost immuno-reactivity, we focus on resetting circadian neuroendocrine events that organize overall global immunophysiology to treat immuno-suppressed states. Similarly, autoimmune disorders with genetic components manifest as alterations in the neuroendocrine axis which in turn potentiate the underlying disorder.
Consequently, autoimmune diseases may be improved by appropriately resetting specific aberrations in the circadian neuroendocrine axis. Our interventions are not just pharmaceutical compounds but rather therapeutic treatment regimens employing such compounds in a particular manner to reprogram the master control centers in the brain for the production of whole-body immunological status.
SELECTED PUBLICATIONS
Gaziano JM, Cincotta AH, O'Connor CM, Ezrokhi M, Rutty D, Ma ZJ, Scranton RE.
Randomized clinical trial of quick-release bromocriptine among patients with type 2 diabetes on overall safety and cardiovascular outcomes.
Diabetes Care. 2010 Jul;33(7):1503-8. Epub 2010 Mar 23.
Scranton R, Cincotta A.
Bromocriptine--unique formulation of a dopamine agonist for the treatment of type 2 diabetes.
Expert Opin Pharmacother. 2010 Feb;11(2):269-79.
Liang Y, Cincotta AH.
Increased responsiveness to the hyperglycemic, hyperglucagonemic and hyperinsulinemic effects of circulating norepinephrine in ob/ob mice.
Int J Obes Relat Metab Disord. 2001 May;25(5):698-704.
Jetton TL, Liang Y, Cincotta AH.
Systemic treatment with sympatholytic dopamine agonists improves aberrant beta-cell hyperplasia and GLUT2, glucokinase, and insulin immunoreactive levels in ob/ob mice.
Metabolism. 2001 Nov;50(11):1377-84.
Boundy VA, Cincotta AH.
Hypothalamic adrenergic receptor changes in the metabolic syndrome of genetically obese (ob/ob) mice.
Am J Physiol Regul Integr Comp Physiol. 2000 Aug;279(2):R505-14.
Kraszewski KZ, Cincotta AH.
Increased responsiveness of ventromedial hypothalamic neurons to norepinephrine
in obese versus lean mice: relation to the metabolic syndrome.
Int J Mol Med. 2000 Apr;5(4):349-55.
Scislowski PW, Tozzo E, Zhang Y, Phaneuf S, Prevelige R, Cincotta AH.
Biochemical mechanisms responsible for the attenuation of diabetic and obese conditions in ob/ob mice treated with dopaminergic agonists.
Int J Obes Relat Metab Disord. 1999 Apr;23(4):425-31.
Cincotta L, Szeto D, Lampros E, Hasan T, Cincotta AH.
Benzophenothiazine and benzoporphyrin derivative combination phototherapy effectively eradicates large murine sarcomas.
Photochem Photobiol. 1996 Feb;63(2):229-37.
Cincotta L, Foley JW, MacEachern T, Lampros E, Cincotta AH.
Novel photodynamic effects of a benzophenothiazine on two different murine sarcomas.
Cancer Res. 1994 Mar 1;54(5):1249-58.
Cincotta L, Foley JW, Cincotta AH.
Phototoxicity, redox behavior, and pharmacokinetics of benzophenoxazine analogues in EMT-6 murine sarcoma cells.
Cancer Res. 1993 Jun 1;53(11):2571-80.
