PMID- 10999789
OWN - NLM
STAT- MEDLINE
DCOM- 20001016
LR  - 20111117
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 85
IP  - 9
DP  - 2000 Sep
TI  - Recombinant human insulin-like growth factor I treatment for 1 week improves 
      metabolic control in type 2 diabetes by ameliorating hepatic and muscle insulin 
      resistance.
PG  - 3077-84
AB  - The administration of recombinant human insulin-like growth factor I (rhIGF-I) 
      reduces hyperglycemia and insulin requirements in subjects with severe insulin 
      resistance syndromes and in patients with type 2 diabetes mellitus (T2DM). 
      However, the mechanisms responsible for the improved metabolic control are 
      incompletely understood. One proposed mechanism is that rhIGF-I therapy in T2DM 
      may bypass early defects in insulin action (i.e. signal transduction), leading to 
      improved hepatic and/or peripheral insulin sensitivity. To test this hypothesis, 
      we used the euglycemic insulin clamp to measure the response to 7 days of rhIGF-I 
      therapy (80 microg/kg, sc, twice daily) in eight poorly controlled T2DM subjects. 
      rhIGF-I significantly improved fasting (203 +/- 12 vs. 134 +/- 14 mg/dL; P < 
      0.01) and day-long (0800-1700 h; 234 +/- 11 vs. 153 +/- 10 mg/dL; P < 0.01) 
      plasma glucose levels. Basal endogenous glucose production decreased from 3.2 +/- 
      0.2 to 2.7 +/- 0.2 mg/kg lean body mass x min (P < 0.03) despite a concomitant 
      decline in the fasting plasma insulin concentration from 13 +/- 5 to 5 +/- 1 
      microU/mL (P < 0.01). The decrement in basal endogenous glucose production was 
      closely correlated with the decrement in fasting plasma glucose concentration (r 
      = 0.78; P < 0.01). Whole body insulin-stimulated glucose disposal increased by 
      27% (from 5.6 +/- 0.8 to 7.1 +/- 0.8 mg/kg lean body mass x min; P < 0.01), but 
      remained well below that observed in age- and weight-matched healthy subjects. 
      The effects of rhIGF-I on endogenous glucose production and peripheral insulin 
      sensitivity resemble those observed with intensified insulin regimens in T2DM. We 
      conclude that 7 days of sc rhIGF-I improves glucose control by improving hepatic 
      and muscle insulin sensitivity, but it remains markedly abnormal. This indicates 
      that an intrinsic defect(s) responsible for insulin resistance in T2DM cannot be 
      overcome by rhIGF-I treatment.
FAU - Cusi, K
AU  - Cusi K
AD  - Department of Medicine, University of Texas Health Science Center, San Antonio 
      78284, USA. cusi@uthscsa.edu
FAU - DeFronzo, R
AU  - DeFronzo R
LA  - eng
GR  - RR-01346/RR/NCRR NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Blood Glucose)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Hormones)
RN  - 0 (Insulin)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 0 (Lactates)
RN  - 0 (Recombinant Proteins)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Blood Glucose/metabolism
MH  - Diabetes Mellitus, Type 2/*drug therapy/*metabolism
MH  - Fatty Acids, Nonesterified/blood
MH  - Female
MH  - Glucose Tolerance Test
MH  - Hemodynamics/drug effects
MH  - Hormones/blood
MH  - Humans
MH  - Insulin/physiology
MH  - Insulin Resistance/*physiology
MH  - Insulin-Like Growth Factor Binding Protein 3/blood
MH  - Insulin-Like Growth Factor I/adverse effects/metabolism/*therapeutic use
MH  - Lactates/blood
MH  - Liver/drug effects/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Muscle, Skeletal/drug effects/*metabolism
MH  - Recombinant Proteins/therapeutic use
EDAT- 2000/09/22 11:00
MHDA- 2000/10/21 11:01
CRDT- 2000/09/22 11:00
PHST- 2000/09/22 11:00 [pubmed]
PHST- 2000/10/21 11:01 [medline]
PHST- 2000/09/22 11:00 [entrez]
AID - 10.1210/jcem.85.9.6827 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2000 Sep;85(9):3077-84. doi: 10.1210/jcem.85.9.6827.