The GluCre‐ROSA26EYFP mouse: A new model for easy identification of living pancreatic α‐cells

The control of glucagon secretion by pancreatic α‐cells is poorly understood, largely because of the difficulty to recognize living α‐cells. We describe a new mouse model, referred to as GluCre‐ROSA26EYFP (or GYY), allowing easy α‐cell identification because of specific expression of EYFP. GYY mice displayed normal glycemic control during a fasting/refeeding test or intraperitoneal insulin injection. Glucagon secretion by isolated islets was normally inhibited by glucose and stimulated by adrenaline. [Ca2+]c responses to arginine, adrenaline, diazoxide and tolbutamide, were similar in GYY and control mice. Hence, this new mouse model is a reliable and powerful tool to specifically study α‐cells.

[1]  Philippe Soriano Generalized lacZ expression with the ROSA26 Cre reporter strain , 1999, Nature Genetics.

[2]  D. Pipeleers,et al.  A new in vitro model for the study of pancreatic A and B cells. , 1985, Endocrinology.

[3]  P. Cryer,et al.  Hypoglycaemia: The limiting factor in the glycaemic management of Type I and Type II Diabetes* , 2002, Diabetologia.

[4]  P. Arkhammar,et al.  Functional identification and monitoring of individual α and β cells in cultured mouse islets of Langerhans , 2004, Acta Diabetologica.

[5]  C. Wollheim,et al.  Islet β-cell secretion determines glucagon release from neighbouring α-cells , 2003, Nature Cell Biology.

[6]  C. Sempoux,et al.  Pancreatic B-cell proliferation in persistent hyperinsulinemic hypoglycemia of infancy: an immunohistochemical study of 18 cases. , 1998, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[7]  A. Arredouani,et al.  Atypical Ca2+‐induced Ca2+ release from a sarco‐endoplasmic reticulum Ca2+‐ATPase 3‐dependent Ca2+ pool in mouse pancreatic β‐cells , 2004, The Journal of physiology.

[8]  B. Soria,et al.  Different effects of tolbutamide and diazoxide in alpha, beta-, and delta-cells within intact islets of Langerhans. , 1999, Diabetes.

[9]  Erik Gylfe,et al.  Involvement of α1 and β-adrenoceptors in adrenaline stimulation of the glucagon-secreting mouse α-cell , 2004, Naunyn-Schmiedeberg's Archives of Pharmacology.

[10]  H. Johansson,et al.  The actions of arginine and glucose on glucagon secretion are mediated by opposite effects on cytoplasmic Ca2+. , 1987, Biochemical and biophysical research communications.

[11]  P. Lund,et al.  Cytoplasmic Ca2+ oscillations in pancreatic ß-cells , 1992 .

[12]  P. Herrera Defining the cell lineages of the islets of Langerhans using transgenic mice. , 2002, The International journal of developmental biology.

[13]  L. Eliasson,et al.  Tight Coupling Between Electrical Activity and Exocytosis in Mouse Glucagon-Secreting-Cells , 2000 .

[14]  P. Gilon,et al.  Influence of cell number on the characteristics and synchrony of Ca2+ oscillations in clusters of mouse pancreatic islet cells , 1999, The Journal of physiology.

[15]  Lena Eliasson,et al.  Capacitance measurements of exocytosis in mouse pancreatic α‐, β‐ and δ‐cells within intact islets of Langerhans , 2004, The Journal of physiology.

[16]  M. Ravier,et al.  FoxO1 Is Required for the Regulation of Preproglucagon Gene Expression by Insulin in Pancreatic αTC1-9 Cells* , 2006, Journal of Biological Chemistry.

[17]  K. Kaestner,et al.  Imaging pancreatic β-cells in the intact pancreas , 2006 .

[18]  L. Eliasson,et al.  Tight coupling between electrical activity and exocytosis in mouse glucagon-secreting alpha-cells. , 2000, Diabetes.

[19]  P. Gilon,et al.  Emptying of Intracellular Ca2+ Stores Stimulates Ca2+ Entry in Mouse Pancreatic β‐Cells by Both Direct and Indirect Mechanisms , 1997, The Journal of physiology.

[20]  G. Bell,et al.  Transgenic mice with green fluorescent protein-labeled pancreatic β-cells , 2003 .

[21]  Gerich Je Physiology of glucagon. , 1981 .

[22]  P. Herrera,et al.  Adult insulin- and glucagon-producing cells differentiate from two independent cell lineages. , 2000, Development.

[23]  D. Hanahan,et al.  Of Mice and MEN1: Insulinomas in a Conditional Mouse Knockout , 2003, Molecular and Cellular Biology.

[24]  Myriam Nenquin,et al.  In vivo and in vitro glucose-induced biphasic insulin secretion in the mouse: pattern and role of cytoplasmic Ca2+ and amplification signals in beta-cells. , 2006, Diabetes.

[25]  K. Kaestner,et al.  Foxa2 is required for the differentiation of pancreatic α-cells , 2005 .

[26]  H. Katagiri,et al.  Cell type-specific activation of metabolism reveals that β-cell secretion suppresses glucagon release from α-cells in rat pancreatic islets , 2006 .

[27]  R. Unger,et al.  Glucagon physiology and pathophysiology in the light of new advances , 1985, Diabetologia.

[28]  E. Vieira,et al.  A store-operated mechanism determines the activity of the electrically excitable glucagon-secreting pancreatic alpha-cell. , 2004, Cell calcium.

[29]  R. Rizza,et al.  Lack of suppression of glucagon contributes to postprandial hyperglycemia in subjects with type 2 diabetes mellitus. , 2000, The Journal of clinical endocrinology and metabolism.

[30]  J. Gerich,et al.  Physiology of glucagon. , 1981, International review of physiology.

[31]  M. Magnuson,et al.  Dual Roles for Glucokinase in Glucose Homeostasis as Determined by Liver and Pancreatic β Cell-specific Gene Knock-outs Using Cre Recombinase* , 1999, The Journal of Biological Chemistry.

[32]  N. Diamant,et al.  Electrophysiological characterization of pancreatic islet cells in the mouse insulin promoter-green fluorescent protein mouse. , 2005, Endocrinology.

[33]  M. Ravier,et al.  Glucose or Insulin, but not Zinc Ions, Inhibit Glucagon Secretion From Mouse Pancreatic α-Cells , 2005 .

[34]  J. Gromada,et al.  Uptake and Release of Ca2+ by the Endoplasmic Reticulum Contribute to the Oscillations of the Cytosolic Ca2+ Concentration Triggered by Ca2+ Influx in the Electrically Excitable Pancreatic B-cell* , 1999, The Journal of Biological Chemistry.

[35]  Shankar Srinivas,et al.  Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus , 2001, BMC Developmental Biology.

[36]  J. Gromada,et al.  α-Cells of the Endocrine Pancreas: 35 Years of Research but the Enigma Remains. , 2007, Endocrine reviews.

[37]  H. Johansson,et al.  Cyclic AMP raises cytoplasmic calcium in pancreatic alpha 2-cells by mobilizing calcium incorporated in response to glucose. , 1989, Cell calcium.