Abstract
Insulin signaling is initiated by the activation of the insulin receptor (IR) through autophosphorylation of the tyrosine residue in the IR, and then many signaling molecules including IR substrate 1 and 2, phosphoinositide-3-kinase (PI3K) and AKT/protein kinase B (PKB) are involved to modulate downstream signaling pathways. This chapter focuses on the role of PI3K and AKT/PKB in insulin signaling related to pathophysiology in type 2 diabetes mellitus, non-alcoholic fatty liver disease, and liver cancer. To understand the physiologic role of the signaling molecules in insulin action and glucose homeostasis, the chapter reviews the biochemical characteristics of the PI3K and AKT kinases. The secretion of insulin and glucagon are tightly regulated to modulate gluconeogenesis and lipogenesis in hepatocytes, and dysregulation of the proximal signaling pathways of the ligands results in the hyperglycemia and hyperlipidemia seen in metabolic diseases.
Original language | English (US) |
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Title of host publication | The Liver |
Subtitle of host publication | Biology and Pathobiology |
Publisher | wiley |
Pages | 485-495 |
Number of pages | 11 |
ISBN (Electronic) | 9781119436812 |
ISBN (Print) | 9781119436829 |
DOIs | |
State | Published - Jan 24 2020 |
Keywords
- Biochemical characteristics
- Gluconeogenesis
- Hepatocytes
- Insulin-mediated AKT signaling
- Insulin-mediated phosphoinositide-3-kinase signaling
- Lipogenesis
- Liver cancer
- Non-alcoholic fatty liver disease
- Pathophysiologic symptoms
- Type 2 diabetes mellitus
ASJC Scopus subject areas
- General Medicine