PMID- 29672742
OWN - NLM
STAT- MEDLINE
DCOM- 20190104
LR  - 20210206
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 103
IP  - 7
DP  - 2018 Jul 1
TI  - Older Subjects With beta-Cell Dysfunction Have an Accentuated Incretin Release.
PG  - 2613-2619
LID - 10.1210/jc.2018-00260 [doi]
AB  - OBJECTIVE: Insulin secretion (IS) declines with age, which increases the risk of 
      impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) in older 
      adults. IS is regulated by the incretin hormones glucagon-like peptide 1 (GLP-1) 
      and glucose-dependent insulinotropic peptide (GIP). Here we tested the hypotheses 
      that incretin release is lower in older adults and that this decline is 
      associated with beta-cell dysfunction. RESEARCH DESIGN: A total of 40 young (25 +/- 3 
      years) and 53 older (74 +/- 7 years) lean nondiabetic subjects underwent a 2-hour 
      oral glucose tolerance test (OGTT). Based on the OGTT, subjects were divided into 
      three groups: young subjects with normal glucose tolerance (Y-NGT; n = 40), older 
      subjects with normal glucose tolerance (O-NGT; n = 32), and older subjects with 
      IGT (O-IGT; n = 21). MAIN OUTCOME MEASURES: Plasma insulin, C-peptide, GLP-1, and 
      GIP concentrations were measured every 15 to 30 minutes. We quantitated insulin 
      sensitivity (Matsuda index) and insulin secretory rate (ISR) by deconvolution of 
      C-peptide with the calculation of beta-cell glucose sensitivity. RESULTS: Matsuda 
      index, early phase ISR (0 to 30 minutes), and parameters of beta-cell function were 
      lower in O-IGT than in Y-NGT subjects but not in O-NGT subjects. GLP-1 
      concentrations were elevated in both older groups [GLP-1 area under the curve 
      (AUC)0-120 was 2.8 +/- 0.1 in Y-NGT, 3.8 +/- 0.5 in O-NGT, and 3.7 +/- 0.4 nmol/L∙120 
      minutes in O-IGT subjects; P < 0.05], whereas GIP secretion was higher in O-NGT 
      than in Y-NGT subjects (GIP AUC0-120 was 4.7 +/- 0.3 in Y-NGT, 6.0 +/- 0.4 in O-NGT, 
      and 4.8 +/- 0.3 nmol/L∙120 minutes in O-IGT subjects; P < 0.05). CONCLUSIONS: Aging 
      is associated with an exaggerated GLP-1 secretory response. However, it was not 
      sufficient to increase insulin first-phase release in O-IGT and overcome insulin 
      resistance.
FAU - de Jesus Garduno-Garcia, Jose
AU  - de Jesus Garduno-Garcia J
AD  - Diabetes Division, University of Texas Health Science Center, San Antonio, Texas.
AD  - Texas Diabetes Institute, San Antonio, Texas.
FAU - Gastaldelli, Amalia
AU  - Gastaldelli A
AD  - Diabetes Division, University of Texas Health Science Center, San Antonio, Texas.
AD  - Institute of Clinical Physiology, Pisa, Italy.
FAU - DeFronzo, Ralph A
AU  - DeFronzo RA
AD  - Diabetes Division, University of Texas Health Science Center, San Antonio, Texas.
AD  - Texas Diabetes Institute, San Antonio, Texas.
FAU - Lertwattanarak, Raweewan
AU  - Lertwattanarak R
AD  - Diabetes Division, University of Texas Health Science Center, San Antonio, Texas.
AD  - Texas Diabetes Institute, San Antonio, Texas.
FAU - Holst, Jens J
AU  - Holst JJ
AD  - University of Copenhagen, Copenhagen, Denmark.
FAU - Musi, Nicolas
AU  - Musi N
AD  - Diabetes Division, University of Texas Health Science Center, San Antonio, Texas.
AD  - San Antonio Geriatric Research, Education and Clinical Center, San Antonio, 
      Texas.
AD  - Sam and Ann Barshop Institute for Longevity and Aging Studies, University of 
      Texas Health Science Center, San Antonio, Texas.
LA  - eng
GR  - P30 AG013319/AG/NIA NIH HHS/United States
GR  - K23 AG030979/AG/NIA NIH HHS/United States
GR  - R01 DK089229/DK/NIDDK NIH HHS/United States
GR  - R01 DK080157/DK/NIDDK NIH HHS/United States
GR  - UL1 TR000149/TR/NCATS NIH HHS/United States
GR  - P30 AG044271/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Blood Glucose)
RN  - 0 (C-Peptide)
RN  - 0 (Incretins)
RN  - 0 (Insulin)
RN  - 59392-49-3 (Gastric Inhibitory Polypeptide)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aging/*metabolism
MH  - Blood Glucose/metabolism
MH  - C-Peptide/blood
MH  - Female
MH  - Gastric Inhibitory Polypeptide/blood
MH  - Glucagon-Like Peptide 1/blood
MH  - Glucose Intolerance/*blood
MH  - Glucose Tolerance Test
MH  - Humans
MH  - Incretins/*metabolism
MH  - Insulin/blood
MH  - Insulin Resistance
MH  - Insulin Secretion
MH  - Insulin-Secreting Cells/*metabolism
MH  - Male
PMC - PMC6669818
EDAT- 2018/04/20 06:00
MHDA- 2019/01/05 06:00
PMCR- 2019/04/16
CRDT- 2018/04/20 06:00
PHST- 2018/02/01 00:00 [received]
PHST- 2018/04/11 00:00 [accepted]
PHST- 2018/04/20 06:00 [pubmed]
PHST- 2019/01/05 06:00 [medline]
PHST- 2018/04/20 06:00 [entrez]
PHST- 2019/04/16 00:00 [pmc-release]
AID - 4970150 [pii]
AID - jcem_201800260 [pii]
AID - 10.1210/jc.2018-00260 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2018 Jul 1;103(7):2613-2619. doi: 10.1210/jc.2018-00260.