Elevated NEFA levels impair glucose effectiveness by increasing net hepatic glycogenolysis.
Diabetologia
; 55(11): 3021-8, 2012 Nov.
Article
in En
| MEDLINE
| ID: mdl-22847060
ABSTRACT
AIMS/HYPOTHESIS:
Acute hyperglycaemia rapidly suppresses endogenous glucose production (EGP) in non-diabetic individuals, mainly by inhibiting glycogenolysis. Loss of this 'glucose effectiveness' contributes to fasting hyperglycaemia in type 2 diabetes. Elevated NEFA levels characteristic of type 2 diabetes impair glucose effectiveness, although the mechanism is not fully understood. Therefore we examined the impact of increasing NEFA levels on the ability of hyperglycaemia to regulate pathways of EGP.METHODS:
We performed 4 h 'pancreatic clamp' studies (somatostatin; basal glucagon/growth hormone/insulin) in seven non-diabetic individuals. Glucose fluxes (D-[6,6-(2)H(2)]glucose) and hepatic glycogen concentrations ((13)C magnetic resonance spectroscopy) were quantified under three conditions euglycaemia, hyperglycaemia and hyperglycaemia with elevated NEFA (HY-NEFA).RESULTS:
EGP was suppressed by hyperglycaemia, but not by HY-NEFA. Hepatic glycogen concentration decreased ~14% with prolonged fasting during euglycaemia and increased by ~12% with hyperglycaemia. In contrast, raising NEFA levels in HY-NEFA caused a substantial ~23% reduction in hepatic glycogen concentration. Moreover, rates of gluconeogenesis were decreased with hyperglycaemia, but increased with HY-NEFA. CONCLUSIONS/INTERPRETATION:
Increased NEFA appear to profoundly blunt the ability of hyperglycaemia to inhibit net glycogenolysis under basal hormonal conditions.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Blood Glucose
/
Diabetes Mellitus, Type 2
/
Glycogenolysis
/
Fatty Acids, Nonesterified
/
Hyperglycemia
Limits:
Adult
/
Humans
/
Male
Language:
En
Journal:
Diabetologia
Year:
2012
Type:
Article
Affiliation country:
United States