General Information:

Id: 897 (click here to show other Interactions for entry)
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mammalia
article
Reference: Milne JC et al.(2007) Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 450: 712-716 [PMID: 18046409]

Interaction Information:

Comment The small molecule activators of SIRT1, including SRT1720, bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates.
Formal Description
Interaction-ID: 5302

drug/chemical compound

SRT1720

interacts (colocalizes) with

gene/protein

SIRT1

Comment The small molecule activators of SIRT1, including SRT1720, bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates.
Formal Description
Interaction-ID: 5311

drug/chemical compound

SRT1720

increases_activity of

gene/protein

SIRT1

Comment In diet-induced obesity (DIO) mice SRT1720 significantly reduced the hyperinsulinemia after 4 weeks, but it did not reduce the insulin levels in mice fed a normal chow diet that are not insulin resistant.
Formal Description
Interaction-ID: 5314

gene/protein

SIRT1

decreases_activity of

phenotype

increased circulating insulin level

in diet-induced obesity mice
Comment In diet-induced obesity (DIO) mice SRT1720 significantly reduced the hyperinsulinemia after 4 weeks, but it did not reduce the insulin levels in mice fed a normal chow diet that are not insulin resistant.
Formal Description
Interaction-ID: 5317

gene/protein

SIRT1

NOT affects_quantity of

complex/PPI

Insulin

in non-insulin resistant chow-fed mice
Comment As observed in calorie restriction, SRT1720 treatment (10 weeks) increases mitochondrial capacity by 15% in gastrocnemius muscle as measured by citrate synthase activity.
Formal Description
Interaction-ID: 5318

gene/protein

SIRT1

increases_activity of

gene/protein

CS

in gastrocnemius muscle
Drugbank entries Show/Hide entries for CS
Comment To study SRT1720 in a genetic model of type 2 diabetes, Lep ob/ob mice were placed on a high-fat diet to induce a diabetic state and then dosed with SRT1720. SRT1720 treatment significantly reduced fasting blood glucose to near normal levels after 1 week.
Formal Description
Interaction-ID: 5320

gene/protein

SIRT1

decreases_quantity of

drug/chemical compound

Glucose

in blood; in diabetic Lep ob/ob mice
Comment In genetically obese Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators (SRT1720) improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver.
Formal Description
Interaction-ID: 5331

gene/protein

SIRT1

decreases_activity of

disease

Insulin resistance

in adipose tissue, in skeletal muscle, in liver; in Zucker fa/fa rats
Comment SRT501, a much less potent SIRT1 activator, also lowered fasting blood glucose in Lep ob/ob mice after 3 weeks (1,000 mg per kg (body weight)) and in DIO mice after 4 weeks (500 mg per kg (bodyweight)) of oral dosin.
Formal Description
Interaction-ID: 50433

drug/chemical compound

SRT501

increases_activity of

gene/protein

SIRT1