Glucose concentration and AMP-dependent kinase activation regulate expression of insulin receptor family members in rat islets and INS-1E beta cells.
OBJECTIVE
Glucose and the peptide growth factors insulin, IGF-I and IGF-II strongly regulate beta cell mass. Furthermore, beta cell expression of IGF-I receptor (Igf1r) and insulin receptor (Insr) is mandatory for several steps of insulin secretion.


METHODS
We hypothesised that glucose concentration might regulate expression of Igf1r, Insr and insulin receptor-related receptor (Insrr) in islets and beta cells. Moreover, since the ratio of ATP:ADP is the most important intracellular mechanism involved in insulin secretion, and since depletion of ATP leads to AMP accumulation, we evaluated the role of AMP-activated protein kinase (AMPK) in glucose-dependent receptor regulation.


RESULTS
In rat islets, high glucose exposure (25 mmol/l) increased gene expression of Igf1r, Insr and Insrr but also of the metabolic glycolysis gene liver-type pyruvate kinase (Pklr) compared with intermediate (6.2 mmol/l) or low glucose concentration (1.6 mmol/l) after 24 h. In rat INS-1E beta cells, only Pklr expression was suppressed by low glucose as in islets, while Insr and Insrr were suppressed by high and increased by low glucose levels. Igf1r expression was suppressed by both high- and low- glucose concentration. Activation of AMPK by 5-amino-imidazolecarboxamide riboside (AICAR, 0.5 mmol/l) suppressed Pklr expression, but strongly stimulated gene expression of Igf1r, Insr and Insrr. Protein expression of IR and IGF-IR reflected glucose and AICAR-regulated mRNA expression of both receptors in INS-1E cells.


CONCLUSIONS
We conclude that glucose directly interacts with islet and beta cell expression of growth factor receptors that are mandatory for both beta cell growth and insulin secretion. Stimulation of Igf1r and Insr gene expression by the AMPK-activator AICAR might indicate involvement of AMPK in the regulation of Igf1r, Insr and Insrr expression in beta cells.
Raile
K
K
University Hospital for Children and Adolescents, Oststr. 21-25, 04317 Leipzig, Germany. klemens.raile@medizin.uni-leipzig.de
Klammt
J
J
Laue
S
S
Garten
A
A
Blüher
M
M
Kralisch
S
S
Klöting
N
N
Kiess
W
W
D000818:Animals; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D007340:Insulinoma; D007515:Islets of Langerhans / Q000502:physiology*; D010190:Pancreatic Neoplasms; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000378:metabolism*; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000235:genetics; D011972:Receptor, Insulin / Q000235:genetics*
D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; C118888:AMP-dependent kinase (ATP-forming); D017856:Phosphotransferases (Phosphate Group Acceptor); D005947:Glucose