Research Assistant, Wright State University Department of Physiology and Biophysics
Post-doctoral Fellow, WSU Department of Neuroscience, Cell Biology and Physiology
Research Associate, WSU Department of Pharmacology and Toxicology
Visiting Scientist, Children’s Cancer Institute Australia, University of New South Wales, Sydney, Australia
Research Assistant Professor, Department of Pharmacology & Toxicology, WSU
Assistant Professor, Department of Pharmacology & Toxicology, WSU
Associate Professor, Department of Pharmacology & Toxicology, WSU
Mechanisms of insulin secretion
Our laboratory is interested in the study of anionic mechanisms of insulin secretion and how widely used diuretics and other drugs impact the ability of pancreatic islets to secrete insulin and regulate carbohydrate metabolism directly or indirectly through the regulation of feeding behavior
Our research is primarily focused on the molecular biology, gene expression profile, regulation and physiology of chloride transporters and channels expressed in insulin-secreting β-cells. We are also interested in the role of drugs targeting those transporters and channels on the secretory response and glucose homeostasis. Basically, our interests are centered at the molecular mechanisms involved in the regulation of transporters' gene expression, the intracellular signaling networks leading to transcriptional or post-transcriptional modulation of their expression and function, how these mechanisms interact to modulate insulin secretion in response to nutrients and how primary changes in the secretory response affect satiation and satiety to control energy intake. We use animal or cellular models, which have been genetically modified to lack or over express gene/s of interest. We routinely use functional methods to assess glucose homeostasis, tissue function and hormone secretion. Our research hypotheses are routinely tested at several levels using functional, pharmacological, genetic, molecular and behavioral approaches such as those involving the use of the polymerase chain reaction (PCR), reverse transcription coupled to conventional or quantitative PCR, cloning, sub-cloning, site directed mutagenesis, molecular tagging, gene silencing, gene over expression or immunological imaging techniques and the real time measurement of satiation and satoety responses to food intake.
- The feeding microstructure of male and female mice. Rathod YD and Di Fulvio M. PLoS One (2021) 16(2):e0246569
- Heterogeneous expression of CFTR in insulin-secreting β-cells of the normal human islet. Di Fulvio M, Bogdani M, Velasco M, McMillen TS, Ridaura C, Kelly L, Almutairi MM, Kursan S, Sajib AA, Hiriart M, Aguilar-Bryan L. PLoS One (2020) 15(12):e0242749
- Chloride transporters and channels in β-cell physiology: revisiting a 40-year-old model. Di Fulvio M. Aguilar-Bryan L. (2019) Biochem Soc Trans 47(6):1843-1855.
- Impaired glucose tolerance, glucagon, and insulin responses in mice lacking the loop diuretic-sensitive Nkcc2a transporter. Kelly L, Almutairi MM, Kursan S, Pacheco R, Dias-Junior E, Castrop H, Di Fulvio M. (2019) Am J Physiol 317(4):C843-C856.
- The neuronal K+Cl– co-transporter 2 (Slc12a5) regulates insulin secretion. Kursan S, McMillen T, Beesetty P. Dias-Junior E, Almutairi M, Sajib A, Kozak J, Aguilar-Bryan L and Di Fulvio M. (2017) Sci Reps. 17:1732.
- Survival and growth of C57BL/6J mice lacking the BK channel, Kcnma1: lower adult body weight occurs together with higher body fat. Halm S, Bottomely M, Almutairi M, Di Fulvio M, and Halm D. (2017) Physiol Reps 5:e13137.
- Plasma membrane targeting of endogenous NKCC2 in COS7 cells bypasses functional Golgi cisternae and complex N-glycosylation. Singh R, Kursan S, Almiahoub MY, Almutairi MM, Garzón-Muvdi T, Alvarez-Leefmans FJ and Di Fulvio M. (2017) Front Cell Dev 4:150, doi: 10.3389/fcell.2016.00150.
- A highly efficient strategy to determine genotypes of genetically engineered mice using genomic DNA purified from hair roots. Otaño-Rivera VE, Boakye A, Grobe N, Almutairi MM, Kursan S, Mattis LK, Castrop H, Gurley SB, Elased KM, Boivin GP and Di Fulvio M. (2016) Lab Anim doi: 10.1177/0023677216646088.
- Increased Slc12a1 expression in β-cells and improved glucose disposal in Slc12a2 heterozygous mice. Alshahrani S, Almutairi MM, Kursan S, Dias-Junior E, Almiahuob MYM, Aguilar-Bryan, L and Di Fulvio, M. (2015) J Endocrinol 227:153-65
- Impact of hybrid and complex N-glycans on the cell surface targeting of the endogenous chloride co-transporter Slc12a2. Singh R, Almutairi M, Pacheco-Andrade R, Almiahoub M and Di Fulvio M (2015) Int J Cell Biol 505294:20.
- Functional and molecular evidence for expression of the renin-angiotensin system (RAS) and a disintegrin and metalloproteinase (ADAM) 17 in COS7 cells. Grobe N, Kashkari N, Chodavarapu H, Somineni HK, Singh R, Di Fulvio M, Elased KM. (2015) Am J Physiol 308:C767-77.
- A molecular analysis of the Na+-dependent cation-chloride cotransporters. Gagnon KB and Di Fulvio M (2013) Cell Physiol Biochem 32(7):14-31
- Enhanced insulin secretion and improved glucose tolerance in mice with homozygous inactivation of the Na+K+2Cl– co-transporter-1. Alshahrani S and Di Fulvio M (2012). J Endocrinol 215:59-70
- Expression of the Slc12a1 gene in pancreatic β-cells: Molecular characterization and in silico analysis. Alshahrani S, Alvarez-Leefmans F and Di Fulvio M (2012) Cell Physiol Biochem 30:95-112.
- Molecular and functional expression of cation-chloride-cotransporters in dorsal root ganglion neurons during postnatal maturation. Mao S, Garzon-Muvdi T, Di Fulvio M, Chen Y, Delpire E, Alvarez FJ and Alvarez-Leefmans FJ. (2012) J Neurophysiol 108:834-852
- KCC2a expression in a primary fetal human lens epithelial cell line, FHL-12. Lauf PK,Di Fulvio M, Srivastava V, Sharma Sand Adragna C. (2012) Cell Physiol Biochem 29(1-2):303-312.
- mTOR/S6K down-regulation accelerates myeloid cell differentiation by increasing PLD2 expression and Fes kinase activation. Di Fulvio M, Grunwald W, Cool D, Gomez-Cambronero J. (2012) J Biol Chem 287:393-407.
- TOR and S6K down-regulate PLD2 basal expression and function. Tabatabaian F, Dougherty K, Di Fulvio M, Gomez-Cambronero J. (2010) J Biol Chem 285:8991-9001.
- PLD2 has both enzymatic and cell proliferation-inducing capabilities that are differentially regulated by phosphorylation and dephosphorylation. Henkels KM, Short S, Peng H-J, Di Fulvio M, Gomez-Cambronero J. (2009) Biochem Biophys Res Commun 389:224-228.
- Tyrosine phosphorylation of Grb2: Role in prolactin/epidermal growth factor crosstalk in mammary epithelial cell growth and differentiation. Haines E, Minoo P, Feng Z, Resalatpanah N, Nie XM, Campiglio M, Alvarez L, Cocolakis E, Ridha M, Di Fulvio M, Gomez-Cambronero J, Lebrun JJ, Ali S. (2009) Mol Cell Biol 29:2505-20.
- Mutation of Y179 on phospholipase D2 (PLD2) affects DNA synthesis in a PI3K-dependent manner. Di Fulvio M, Frondorf K, Gomez-Cambronero J. (2008) Cell Signaling 20:176-185.
- Short-hairpin RNA-mediated stable silencing of Grb2 impairs cell growth and DNA synthesis. Di Fulvio M, Henkels K and Gomez-Cambornero J. (2007) Biochem Biophys Res Commun 357:737-742.
- Phospholipase D (PLD)-derived phosphatidic acid (PA) binds to and activates ribosomal p70S6 kinase (p70S6K). Lehman N, Di Fulvio M, McPhail L, Gomez-Cambronero J. (2007) FASEB J 21:1075-87.
- The Grb2/PLD2 interaction is essential for lipase activity, intracellular localization and signaling, in response to EGF. Di Fulvio M, Frondorf K, Henkels K, Lehman N, Gomez-Cambronero, J. (2007) J Mol Biol 367:814-24.
- Understanding phospholipase D (PLD) using leukocytes: PLD involvement in cell chemotaxis and adhesion. Gomez-Cambronero J. Di Fulvio M, Knapek K. (2007) J Leukoc Biol 82:272-281.
- Phagocyte cell migration is mediated by phospholipases PLD1 and PLD2. Lehman N, Di Fulvio M, McCray N, Campos I, Gomez-Cambronero J. (2006) Blood 108:3564-3572.
- The elucidation of novel SH2 binding sites on PLD2. Di Fulvio M, Lehman N, Lin X, Lopez I, Gómez-Cambronero J. (2006) Oncogene 25:3032-3040.
- Signal transduction mechanisms of K-Cl cotransport regulation and their relationship to disease. Adragna NC, Ferrell CM, Zhang J, Di Fulvio M, Temprana CF, Sharma A, Fyffe REW, Cool DR, Lauf PK. (2006) Acta Physiologica 187:125-139
- Phospholipase D (PLD) gene expression in human neutrophils and HL60 differentiation. Di Fulvio M, Gómez-Cambronero J. (2005) J Leukoc Biol 77:999-1007.
- Regulation of K-Cl cotransport: from function to genes. Adragna NC, Di Fulvio M, Lauf PK. (2004) J Memb Biol 201:109-137
- Ultrastructural localization of thyroid peroxidase, hydrogen peroxide-generating sites, and monoamine oxidase in benign and malignant thyroid diseases. Masini-Repiso AM, Bonaterra M, Spitale L, Di Fulvio M, Bonino MI, Coleoni AH, Orgnero-Gaisan E. (2004) Hum Pathol 35:436-446.
- The nitric oxide signaling pathway regulates K-Cl cotransporters-3 (KCC3a and KCC3b) expression in vascular smooth muscle cells. Di Fulvio M, Lauf PK, Adragna NC. (2003) Nitric Oxide 9:165-171.
- NONOates regulates potassium-chloride cotransporter-1 and 3 mRNA expression in vascular smooth muscle cells. Di Fulvio M, Lauf PK, Sha S, Adragna NC. (2003) Am J Physiol 284:H1686-1692.
- KCl cotransport regulation and protein kinase G in cultured vascular smooth muscle cells. Adragna NC, Zhang J, Di Fulvio M, Lincoln TM, Lauf PK. (2002) J Memb Biol 187:157-165.
- Nitric oxide signaling pathway regulates the potassium-chloride cotransporter-1 mRNA expression in vascular smooth muscle cells. Di Fulvio M, Lauf PK, Adragna NC. (2001) J Biol Chem 276:44534-44540.
- Protein kinase G regulates the potassium-chloride cotransporter (KCC)-4 mRNA expression in primary cultures of rat vascular smooth muscle cells. Di Fulvio M, Lincoln TM, Lauf PK, Adragna NC. (2001) J Biol Chem 276:21046-21052.
- Tri-iodothyronine induces proliferation in cultured bovine thyroid. Evidence for the involvement of epidermal growth factor-associated tyrosine kinase activity. Di Fulvio M, Pellizas CG, Coleoni AH, Masini-Repiso AM. (2000) J Endocrinol 166 173-182.
- Insulin like growth factor-I reduces thyroid hormone receptors in the rat liver. Evidence for a feedback loop regulating the peripheral thyroid hormone action. Pellizas CG, Coleoni AH, Costamagna ME, Di Fulvio M, Masini-Repiso AM. (1998) J Endocrinol 158:87-95, 1998.
- A new point mutation (M313T) in the thyroid hormone receptor b gene in a patient with thyroid hormone resistance. Di Fulvio M, Baranzini S, Chiesa A, Gruñeiro-Papendiek L, Masini-Repiso AM, Targovnik HM. (1997) Thyroid 7:1:43-44
1. Chloride Channels and Transporters in β-cell Physiology. Di Fulvio M, Peter Brown and Lydia Aguilar-Bryan (2014) In: The Islets of Langerhans, Chapter 14 p. 401-451. Ed. Md. Shahidul Islam M.D., Ph.D. Springer Netherlands.
2. The NKCC and NCC genes, an in silico analysis. Di Fulvio M and Alvarez-Leefmans FJ (2009) In: Physiology and Pathology of Chloride Transporters and Channels in the Nervous System. From molecules to diseases. p. 169-208. Eds. Javier Alvarez-Leefmans & Eric Delpire. Elsevier. Academic Press, San Diego, CA.
Clinical Biochemistry, National University of Córdoba, Argentina
Ph.D. Chemical Sciences (Biochemistry), National University of Córdoba, Argentina.