Regulation of α, β and δ-Cells

UNIT of Cell Physiology and Nutrition

Islet Cell Signaling

Regulation of α, β and δ-Cells

Human Nutrition

 

Regulation of alpha, beta and delta-Cells

Regulation of alpha, beta and delta-Cells

Regulation of alpha, beta and delta-Cells

Regulation of alpha, beta and delta-Cells

 

Group leader: IVÁN QUESADA

Blood glucose homeostasis is mainly regulated by the coordinated function of alpha, beta and delta-cells, which coexist within the islet of Langerhans. These cells secrete glucagon, insulin and somatostatin, respectively. In addition to glucose homeostasis, these endocrine cells and their hormones participate in the regulation of energy balance and the homeostasis of carbohydrates, lipids and amino-acids. The appropriate function of these cells is impaired in pathological situations such as diabetes and obesity, which leads to multiple metabolic disorders.

In our group, we particularly focus on the mechanisms and signal transduction pathways that regulate the secretion and function of alpha, beta and delta-cells. We work mainly at the cellular and molecular level. We also study those conditions that lead to their malfunction or compromise their survival such as hyperglycemia or excess of fatty acids, which are associated with diabetes and obesity.

Selected publications:

  • Quesada I, Tuduri E, Ripoll C, Nadal A. (2008) Physiology of the pancreatic alpha-cell and glucagon secretion: role in glucose homeostasis and diabetes. Journal of Endocrinology. 199: 5–19.
  • Tuduri E, Marroquí L, Soriano S, Ropero AB, Batista TM, Piquer S, López-Boado MA, Carneiro EM, Gomis R, Nadal A, and Quesada I. (2009) Inhibitory effects of leptin on the pancreatic alpha-cell function. Diabetes. 58:1616-1624.
  • Soriano S, Gonzalez A, Marroqui L, Tuduri E, Vieira E, Amaral AG, Batista TM, Rafacho A, Boschero AC, Nadal A Carneiro EM, Quesada I. (2010) Reduced insulin secretion in protein malnourished mice is associated to multiple changes in the beta-cell stimulus-secretion coupling. Endocrinology. 151: 3543-3554.
  • Marroquí L, Vieira E, Gonzalez A, Nadal A, Quesada I. (2011) Leptin downregulates expression of the gene encoding glucagon in alphaTC1-9 cells and mouse islets. Diabetologia. 54: 843–851.
  • Vieira E, Marroquí L, Batista TM, Caballero-Garrido E, Carneiro EM, Boschero AC, Nadal A, Quesada I. (2012) The Clock Gene Rev-erb alpha Regulates Pancreatic Beta-Cell Function: Modulation by Leptin and High-Fat Diet. Endocrinology. 153:592-601.
  • Marroquí L, Batista TM, Gonzalez A, Vieira E, Rafacho A, Colleta SJ, Taboga SR, Boschero AC, Nadal A, Carneiro EM, Quesada I. (2012) Functional and structural adaptations in the pancreatic alpha-cell and changes in glucagon signaling during protein malnutrition. Endocrinology. 153: 1663-1672.
  • Gonzalez A, Merino B, Marroqui L, Ñeco P, Alonso-Magdalena P, Vieira E, Caballero-Garrido E, Soriano S, Gomis R, Nadal A, Quesada I. (2013) Insulin hypersecretion in islets from diet-induced hyperinsulinemic female obese mice is associated to several functional adaptations in individual beta-cells. Endocrinology. 154:3515-3524.
  • Rafacho A, Gonçalves-Neto LM, Santos-Silva JC, Alonso-Magdalena P, Merino B, Taboga SR, Carneiro EM, Boschero AC, Nadal A, Quesada I. (2014) Pancreatic alpha-cell dysfunction contributes to the disruption of glucose homeostasis and compensatory insulin hypersecretion in glucocorticoid-treated rats. PLoS One. 9: e93531.
  • Vieira E, Burris TP, Quesada I. (2014) Clock genes, pancreatic function and diabetes. Trends in Molecular Medicine. 20:685-693.
  • Marroqui L, Masini M, Merino B, Grieco FA, Millard I, Dubois C, Quesada I, Marchetti P, Cnop M, Eizirik DL. (2015) Pancreatic Alpha Cells are Resistant to Metabolic Stress-induced Apoptosis in Type 2 Diabetes. EBiomedicine. 2: 378-385.
  • Merino B, Alonso-Magdalena P, Lluesma M, Ñeco P, Gonzalez A, Marroquí L, García-Arévalo M, Nadal A, Quesada I. (2015) Pancreatic alpha-cells from female mice undergo morphofunctional changes during compensatory adaptations of the endocrine pancreas to diet-induced obesity. Scientific Reports. 5:11622.