PMID- 30117761
OWN - NLM
STAT- MEDLINE
DCOM- 20190626
LR  - 20191001
IS  - 1557-8518 (Electronic)
IS  - 1540-4196 (Print)
IS  - 1540-4196 (Linking)
VI  - 16
IP  - 8
DP  - 2018 Oct
TI  - Mixed Meal and Intravenous L-Arginine Tests Both Stimulate Incretin Release 
      Across Glucose Tolerance in Man: Lack of Correlation with beta Cell Function.
PG  - 406-415
LID - 10.1089/met.2018.0022 [doi]
AB  - BACKGROUND: The aims of this study were to 1. define the responses of 
      glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide 
      (GIP), glucagon, and peptide YY (PYY) to an oral meal and to intravenous 
      L-arginine; and 2. examine correlation of enteroendocrine hormones with insulin 
      secretion. We hypothesized a relationship between circulating incretin 
      concentrations and insulin secretion. METHODS: Subjects with normal glucose 
      tolerance (NGT, n = 23), prediabetes (PDM, n = 17), or with type 2 diabetes 
      (T2DM, n = 22) were studied twice, following a mixed test meal (470 kCal) (mixed 
      meal tolerance test [MMTT]) or intravenous L-arginine (arginine maximal 
      stimulation test [AST], 5 g). GLP-1 (total and active), PYY, GIP, glucagon, and beta 
      cell function were measured before and following each stimulus. RESULTS: Baseline 
      enteroendocrine hormones differed across the glucose tolerance (GT) spectrum, 
      T2DM generally >NGT and PDM. In response to MMTT, total and active GLP-1, GIP, 
      glucagon, and PYY increased in all populations. The incremental 
      area-under-the-curve (0-120 min) of analytes like total GLP-1 were often higher 
      in T2DM compared with NGT and PDM (35-51%; P < 0.05). At baseline glucose, 
      L-arginine increased total and active GLP-1 and glucagon concentrations in all GT 
      populations (all P < 0.05). As expected, the MMTT and AST provoked differential 
      glucose, insulin, and C-peptide responses across GT populations. Baseline or 
      stimulated enteroendocrine hormone concentrations did not consistently correlate 
      with either measure of beta cell function. CONCLUSIONS/INTERPRETATION: Both MMTT and 
      AST resulted in insulin and enteroendocrine hormone responses across GT 
      populations without consistent correlation between release of incretins and 
      insulin, which is in line with other published research. If a defect is in the 
      enteroendocrine/beta cell axis, it is probably reduced response to rather than 
      diminished secretion of enteroendocrine hormones.
FAU - Ruetten, Hartmut
AU  - Ruetten H
AD  - 1 Sanofi-Aventis Deutschland GmbH , Frankfurt, Germany .
FAU - Gebauer, Mathias
AU  - Gebauer M
AD  - 1 Sanofi-Aventis Deutschland GmbH , Frankfurt, Germany .
FAU - Raymond, Ralph H
AU  - Raymond RH
AD  - 2 R-Squared Solutions , Skillman New Jersey.
FAU - Calle, Roberto A
AU  - Calle RA
AD  - 3 Pfizer, Inc. , Cambridge, Massachusetts.
FAU - Cobelli, Claudio
AU  - Cobelli C
AD  - 4 Department of Information Engineering, University of Padova , Padova, Italy .
FAU - Ghosh, Atalanta
AU  - Ghosh A
AD  - 5 Janssen Research and Development , Raritan, New Jersey.
FAU - Robertson, R Paul
AU  - Robertson RP
AD  - 6 Pacific Northwest Diabetes Institute, University of Washington , Seattle, 
      Washington.
FAU - Shankar, Sudha S
AU  - Shankar SS
AD  - 7 Lilly Research Laboratories, Lilly Corporate Center , Indianapolis, Indiana.
FAU - Staten, Myrlene A
AU  - Staten MA
AD  - 8 NIDDK , Bethesda, Maryland.
FAU - Stefanovski, Darko
AU  - Stefanovski D
AD  - 9 School of Veterinary Medicine, University of Pennsylvania , Philadelphia, 
      Pennsylvania.
FAU - Vella, Adrian
AU  - Vella A
AD  - 10 Division of Endocrinology, Mayo Clinic and Foundation , Rochester, Minnesota.
FAU - Wright, Kathryn
AU  - Wright K
AD  - 11 Wright Biomarker Consulting , Gales Ferry, Connecticut.
FAU - Fryburg, David A
AU  - Fryburg DA
AD  - 12 ROI BioPharma Consulting , East Lyme, Connecticut.
CN  - Foundation for the NIH Biomarkers Consortium Beta Cell Project Team
LA  - eng
SI  - ClinicalTrials.gov/NCT01454973
SI  - ClinicalTrials.gov/NCT01663207
SI  - ClinicalTrials.gov/NCT01663220
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20180817
PL  - United States
TA  - Metab Syndr Relat Disord
JT  - Metabolic syndrome and related disorders
JID - 101150318
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (Gastrointestinal Hormones)
RN  - 0 (Insulin)
RN  - 106388-42-5 (Peptide YY)
RN  - 59392-49-3 (Gastric Inhibitory Polypeptide)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 9007-92-5 (Glucagon)
RN  - 94ZLA3W45F (Arginine)
SB  - IM
EIN - Metab Syndr Relat Disord. 2019 Mar;17(2):128. PMID: 30822261
MH  - Administration, Intravenous
MH  - Arginine/*administration & dosage
MH  - Biomarkers/blood
MH  - Blood Glucose/*metabolism
MH  - Cross-Sectional Studies
MH  - Diabetes Mellitus, Type 2/*blood/diagnosis/physiopathology
MH  - *Eating
MH  - Enteroendocrine Cells/*drug effects/metabolism
MH  - Gastric Inhibitory Polypeptide/blood
MH  - Gastrointestinal Hormones/*blood
MH  - Glucagon/blood
MH  - Glucagon-Like Peptide 1/blood
MH  - Humans
MH  - Insulin/blood
MH  - Insulin-Secreting Cells/*drug effects/metabolism
MH  - Peptide YY/blood
MH  - Postprandial Period
MH  - Prediabetic State/*blood/diagnosis/physiopathology
MH  - Time Factors
MH  - United States
PMC - PMC6167614
OTO - NOTNLM
OT  - GLP-1
OT  - arginine
OT  - incretin
OT  - insulin secretion
OT  - meal tolerance test
OT  - type 2 diabetes
COIS- H.R., and M.G., employee and shareholder of Sanofi-Aventis Deutschland GmbH. 
      R.A.C., employee and shareholder of Pfizer. A.G., employee and shareholder of 
      Janssen Pharmaceuticals. S.S.S., employee and shareholder of Eli Lilly and Co. 
      D.A.F., shareholder, Pfizer, Inc. For R.H.R., C.C., R.P.R., M.A.S., D.S., A.V., 
      and K.W. no conflicting financial interests exist.
FIR - Bergman, Richard
IR  - Bergman R
FIR - Calle, Roberto
IR  - Calle R
FIR - Cobelli, Claudio
IR  - Cobelli C
FIR - Farmen, Mark
IR  - Farmen M
FIR - Gosh, Atalanta
IR  - Gosh A
FIR - Irony, Ilan
IR  - Irony I
FIR - Lee, Douglas
IR  - Lee D
FIR - Martin, Frank
IR  - Martin F
FIR - Hersloev, Malene
IR  - Hersloev M
FIR - Jerzy, Kolaczynski
IR  - Jerzy K
FIR - Moran, Stephanie
IR  - Moran S
FIR - Polidori, David
IR  - Polidori D
FIR - Raymond, Ralph
IR  - Raymond R
FIR - Robertson, R Paul
IR  - Robertson RP
FIR - Ruetten, Hartmut
IR  - Ruetten H
FIR - Shankar, Sudha
IR  - Shankar S
FIR - Staten, Myrlene
IR  - Staten M
FIR - Stefanovski, Darko
IR  - Stefanovski D
FIR - Vardanian, Lilit
IR  - Vardanian L
FIR - Vella, Adrian
IR  - Vella A
FIR - Weir, Gordon
IR  - Weir G
FIR - Zakaria, Marjorie
IR  - Zakaria M
FIR - Deeg, Mark
IR  - Deeg M
FIR - Kelley, David
IR  - Kelley D
FIR - Savage, Peter
IR  - Savage P
FIR - Spear, Nicole
IR  - Spear N
FIR - Vassileva, Maria
IR  - Vassileva M
FIR - Whitaker, Sanya
IR  - Whitaker S
EDAT- 2018/08/18 06:00
MHDA- 2019/06/27 06:00
PMCR- 2019/10/01
CRDT- 2018/08/18 06:00
PHST- 2018/08/18 06:00 [pubmed]
PHST- 2019/06/27 06:00 [medline]
PHST- 2018/08/18 06:00 [entrez]
PHST- 2019/10/01 00:00 [pmc-release]
AID - 10.1089/met.2018.0022 [pii]
AID - 10.1089/met.2018.0022 [doi]
PST - ppublish
SO  - Metab Syndr Relat Disord. 2018 Oct;16(8):406-415. doi: 10.1089/met.2018.0022. 
      Epub 2018 Aug 17.