AMPK (5′-AMP-activated protein kinase) is emerging as a metabolic master switch, by which cells in both mammals and lower organisms sense and decode changes in energy status. Changes in AMPK activity have been shown to regulate glucose transport in muscle and glucose production by the liver. Moreover, AMPK appears to be a key regulator of at least one transcription factor linked to a monogenic form of diabetes mellitus. As a result, considerable efforts are now under way to explore the usefulness of AMPK as a therapeutic target for other forms of this disease. Here we review this topic, and discuss new findings which suggest that AMPK may play roles in regulating insulin release and the survival of pancreatic islet β-cells, and nutrient sensing by the brain.
- 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR)
- 5′-AMP-activated protein kinase (AMPK)
- diabetes mellitus
- glucose homoeostasis
- insulin secretion
- pancreatic islet β-cell
Abbreviations used: ACC, acetyl-CoA carboxylase; ACRP30, adipocyte complement-related protein of 30 kDa; AICAR, 5-aminoimidazole-4-carboxamide ribonucleoside; AMPK, 5′-AMP-activated protein kinase; AMPKK, AMPK kinase; [Ca2+]c, cytosolic free Ca2+ concentration; CBS, cystathionine β-synthase; CHO, Chinese hamster ovary; ChREBP, carbohydrate response element binding protein; eIF, eukaryotic initiation factor; FAS, fatty acid synthase; HNF4α, hepatocyte nuclear factor 4α; HSL, hormone sensitive lipase; IRS-1, insulin receptor substrate-1; KATP channel, ATP-sensitive potassium channel; L-PK, liver-type pyruvate kinase; MAPK, mitogen-activated protein kinase; PI3K, phosphoinositode 3′-kinase; PKA, protein kinase A; PKC, protein kinase C; PPARγ, peroxisome proliferator activated receptor γ; SNF-1, sucrose non-fermenting; SREBP, sterol regulatory element binding protein.
- The Biochemical Society, London ©2003