PMID- 17299078
OWN - NLM
STAT- MEDLINE
DCOM- 20070730
LR  - 20240404
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 292
IP  - 6
DP  - 2007 Jun
TI  - Effects on insulin secretion and insulin action of a 48-h reduction of plasma 
      free fatty acids with acipimox in nondiabetic subjects genetically predisposed to 
      type 2 diabetes.
PG  - E1775-81
AB  - Elevated plasma FFA cause beta-cell lipotoxicity and impair insulin secretion in 
      nondiabetic subjects predisposed to type 2 diabetes mellitus [T2DM; i.e., with a 
      strong family history of T2DM (FH+)] but not in nondiabetic subjects without a 
      family history of T2DM. To determine whether lowering plasma FFA with acipimox, 
      an antilipolytic nicotinic acid derivative, may enhance insulin secretion, nine 
      FH+ volunteers were admitted twice and received in random order either acipimox 
      or placebo (double-blind) for 48 h. Plasma glucose/insulin/C-peptide 
      concentrations were measured from 0800 to 2400. On day 3, insulin secretion rates 
      (ISRs) were assessed during a +125 mg/dl hyperglycemic clamp. Acipimox reduced 
      48-h plasma FFA by 36% (P < 0.001) and increased the plasma C-peptide relative to 
      the plasma glucose concentration or DeltaC-peptide/Deltaglucose AUC (+177%, P = 
      0.02), an index of improved beta-cell function. Acipimox improved insulin 
      sensitivity (M/I) 26.1 +/- 5% (P < 0.04). First- (+19 +/- 6%, P = 0.1) and 
      second-phase (+31 +/- 6%, P = 0.05) ISRs during the hyperglycemic clamp also 
      improved. This was particularly evident when examined relative to the prevailing 
      insulin resistance [1/(M/I)], as both first- and second-phase ISR markedly 
      increased by 29 +/- 7 (P < 0.05) and 41 +/- 8% (P = 0.02). There was an inverse 
      correlation between fasting FFA and first-phase ISR (r2 = 0.31, P < 0.02) and 
      acute (2-4 min) glucose-induced insulin release after acipimox (r2 =0.52, P < 
      0.04). In this proof-of-concept study in FH+ individuals predisposed to T2DM, a 
      48-h reduction of plasma FFA improves day-long meal and glucose-stimulated 
      insulin secretion. These results provide additional evidence for the important 
      role that plasma FFA play regarding insulin secretion in FH+ subjects predisposed 
      to T2DM.
FAU - Cusi, Kenneth
AU  - Cusi K
AD  - Diabetes Division, Department of Medicine, The University of Texas Health Science 
      Center at San Antonio, TX 78284-3900, USA. cusi@uthscsa.edu
FAU - Kashyap, Sangeeta
AU  - Kashyap S
FAU - Gastaldelli, Amalia
AU  - Gastaldelli A
FAU - Bajaj, Mandeep
AU  - Bajaj M
FAU - Cersosimo, Eugenio
AU  - Cersosimo E
LA  - eng
GR  - F32 DK061189/DK/NIDDK NIH HHS/United States
GR  - M01-RR-01346/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20070213
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Blood Glucose)
RN  - 0 (C-Peptide)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Hormones)
RN  - 0 (Hypolipidemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Pyrazines)
RN  - K9AY9IR2SD (acipimox)
SB  - IM
MH  - Adult
MH  - Blood Glucose/metabolism
MH  - C-Peptide/blood
MH  - *Circadian Rhythm
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - Fatty Acids, Nonesterified/*antagonists & inhibitors/*blood
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Glucose Clamp Technique
MH  - Hormones/blood
MH  - Humans
MH  - Hyperglycemia/metabolism
MH  - Hypolipidemic Agents/*pharmacology
MH  - Insulin/metabolism/*physiology
MH  - Insulin Secretion
MH  - Male
MH  - Osmolar Concentration
MH  - Pyrazines/*pharmacology
MH  - Time Factors
EDAT- 2007/02/15 09:00
MHDA- 2007/07/31 09:00
CRDT- 2007/02/15 09:00
PHST- 2007/02/15 09:00 [pubmed]
PHST- 2007/07/31 09:00 [medline]
PHST- 2007/02/15 09:00 [entrez]
AID - 00624.2006 [pii]
AID - 10.1152/ajpendo.00624.2006 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2007 Jun;292(6):E1775-81. doi: 
      10.1152/ajpendo.00624.2006. Epub 2007 Feb 13.