Publications & Research
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.
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.
Bromocriptine-QR therapy for the management of type 2 diabetes mellitus: developmental basis and therapeutic profile summary.
Raskin P, Cincotta AH. Expert Review of Endocrinology & Metabolism. 2016 11(2):113-148.
Timed Bromocriptine-QR Therapy Reduces Progression of Cardiovascular Disease and Dysglycemia in Subjects with Well-Controlled Type 2 Diabetes Mellitus.
Chamarthi B, J. Gaziano JM, , Blonde L, Vinik AI, Scranton R, Ezrokhi M, Rutty D, Cincotta AH. J. Diabetes Res. 2015; Volume 2015, Article ID 157698.
Impact of Bromocriptine-QR Therapy on Glycemic Control and Daily Insulin Requirement in Type 2 Diabetes Mellitus Subjects Whose Dysglycemia Is Poorly Controlled on High-Dose Insulin: A Pilot Study.
Roe ED, Chamarthi B, Raskin P. J Diabetes Res. 2015;2015:834903.
Neuroendocrine and metabolic components of dopamine agonist amelioration of metabolic syndrome in SHR rats.
Ezrokhi M, Luo S, Trubitsyna Y, Cincotta AH. Diabetology & Metabolic Syndrome 2014, 6:104
Effect of bromocriptine-QR on glycemic control in subjects with uncontrolled hyperglycemia on one or two oral anti-diabetes agents.
Vinik AI, Cincotta AH, Scranton RE, Bohannon N, Ezrokhi M, Gaziano JM. Endocr Pract. 2012; 18(6):931-43
Effect of Bromocriptine-QR (a Quick-Release Formulation of Bromocriptine Mesylate) on Major Adverse Cardiovascular Events in Type 2 Diabetes Subjects.
Gaziano JM, Cincotta AH, Vinik A, Blonde L, Bohannon N, Scranton R. J Am Heart Assoc. 2012 Oct;1(5):e002279.
Euglycemic Clamp Conditions in Insulin Resistant Hamsters: Bromocriptine as a
Unique Postprandial Insulin Sensitizer.
Ezrokhi M, Luo S, Trubitsyna Y, Cincotta AH. J Diabetes Metab. 2012 S2:007.
Randomized Clinical Trial Assessing the Efficacy and Safety of Bromocriptine-QR when Added to Ongoing Thiazolidinedione Therapy in Patients with Type 2 Diabetes Mellitus.
Florez H, Scranton R, Farwell WR, DeFronzo RA, Ezrokhi M, Gaziano JM, Cincotta AH. J Diabetes Metab 2011 2:142.
Randomized clinical trial of quick-release bromocriptine among patients with type 2 diabetes on overall safety and cardiovascular outcomes.
Gaziano JM, Cincotta AH, O'Connor CM, Ezrokhi M, Rutty D, Ma ZJ, Scranton RE. Diabetes Care. 2010 Jul;33(7):1503-8.
Bromocriptine--unique formulation of a dopamine agonist for the treatment of type 2 diabetes.
Scranton R, Cincotta A. Expert Opin Pharmacother. 2010 Feb;11(2):269-79.
Increased responsiveness to the hyperglycemic, hyperglucagonemic and hyperinsulinemic effects of circulating norepinephrine in ob/ob mice.
Liang Y, Cincotta AH. Int J Obes Relat Metab Disord. 2001 May;25(5):698-704.
Systemic treatment with sympatholytic dopamine agonists improves aberrant beta-cell hyperplasia and GLUT2, glucokinase, and insulin immunoreactive levels in ob/ob mice.
Jetton TL, Liang Y, Cincotta AH. Metabolism. 2001 Nov;50(11):1377-84.
Hypothalamic adrenergic receptor changes in the metabolic syndrome of genetically obese (ob/ob) mice.
Boundy VA, Cincotta AH. Am J Physiol Regul Integr Comp Physiol. 2000 Aug;279(2):R505-14.
Increased responsiveness of ventromedial hypothalamic neurons to norepinephrine
in obese versus lean mice: relation to the metabolic syndrome.
Kraszewski KZ, Cincotta AH. Int J Mol Med. 2000 Apr;5(4):349-55.
Biochemical mechanisms responsible for the attenuation of diabetic and obese conditions in ob/ob mice treated with dopaminergic agonists.
Scislowski PW, Tozzo E, Zhang Y, Phaneuf S, Prevelige R, Cincotta AH. Int J Obes Relat Metab Disord. 1999 Apr;23(4):425-31.
Circadian rhythms regulate the expression of the thrifty genotype/phenotype.
Meier AH, Cincotta AH. Diabetes Rev 1996;4:464-487
Benzophenothiazine and benzoporphyrin derivative combination phototherapy effectively eradicates large murine sarcomas.
Cincotta L, Szeto D, Lampros E, Hasan T, Cincotta AH. Photochem Photobiol. 1996 Feb;63(2):229-37.
Novel photodynamic effects of a benzophenothiazine on two different murine sarcomas.
Cincotta L, Foley JW, MacEachern T, Lampros E, Cincotta AH. Cancer Res. 1994 Mar 1;54(5):1249-58.
Phototoxicity, redox behavior, and pharmacokinetics of benzophenoxazine analogues in EMT-6 murine sarcoma cells.
Cincotta L, Foley JW, Cincotta AH. Cancer Res. 1993 Jun 1;53(11):2571-80.