Targeting hepatic glucokinase to treat diabetes with TTP399, a hepatoselective glucokinase activator
نویسندگان
چکیده
منابع مشابه
Targeting Hepatic Glucokinase in Type 2 Diabetes
Glucokinase (hexokinase IV) has a major role in the control of blood glucose homeostasis because it is the predominant hexokinase expressed in the liver, has a very high control strength on hepatic glucose disposal (1), and is the glucose sensor for insulin secretion in pancreatic -cells (2). Glucokinase is currently considered a strong candidate target for antihyperglycemic drugs for type 2 di...
متن کاملThe Hepatoselective Glucokinase Activator PF-04991532 Ameliorates Hyperglycemia without Causing Hepatic Steatosis in Diabetic Rats
Hyperglycemia resulting from type 2 diabetes mellitus (T2DM) is the main cause of diabetic complications such as retinopathy and neuropathy. A reduction in hyperglycemia has been shown to prevent these associated complications supporting the importance of glucose control. Glucokinase converts glucose to glucose-6-phosphate and determines glucose flux into the β-cells and hepatocytes. Since acti...
متن کاملDecreased expression of hepatic glucokinase in type 2 diabetes
BACKGROUND/OBJECTIVES Increased endogenous glucose production is a hallmark of type 2 diabetes. Evidence from animal models has suggested that a likely cause of this is increased mRNA expression of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase (encoded by G6PC, PCK1 and PCK2). But another contributing factor may be decreased liver glucokinase (encoded by GCK). METHODS We examine...
متن کاملEffects of a glucokinase activator on hepatic intermediary metabolism: study with 13C-isotopomer-based metabolomics.
GKAs (glucokinase activators) are promising agents for the therapy of Type 2 diabetes, but little is known about their effects on hepatic intermediary metabolism. We monitored the fate of (13)C-labelled glucose in both a liver perfusion system and isolated hepatocytes. MS and NMR spectroscopy were deployed to measure isotopic enrichment. The results demonstrate that the stimulation of glycolysi...
متن کاملGlucokinase Activators for Diabetes Therapy
Type 2 diabetes is characterized by elevated blood glucose levels resulting from a pancreatic b-cell secretory insufficiency combined with insulin resistance, most significantly manifested in skeletal muscle and liver (1). If untreated, diabetic complications develop that cause loss of vision, peripheral neuropathy, impaired kidney function, heart disease, and stroke. The disease has a polygeni...
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ژورنال
عنوان ژورنال: Science Translational Medicine
سال: 2019
ISSN: 1946-6234,1946-6242
DOI: 10.1126/scitranslmed.aau3441