PMID- 30523024
OWN - NLM
STAT- MEDLINE
DCOM- 20190826
LR  - 20240207
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 68
IP  - 3
DP  - 2019 Mar
TI  - Peripheral Mechanisms Mediating the Sustained Antidiabetic Action of FGF1 in the 
      Brain.
PG  - 654-664
LID - 10.2337/db18-0498 [doi]
AB  - We recently reported that in rodent models of type 2 diabetes (T2D), a single 
      intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) 
      induces remission of hyperglycemia that is sustained for weeks. To clarify the 
      peripheral mechanisms underlying this effect, we used the Zucker diabetic fatty 
      fa/fa rat model of T2D, which, like human T2D, is characterized by progressive 
      deterioration of pancreatic beta-cell function after hyperglycemia onset. We report 
      that although icv FGF1 injection delays the onset of beta-cell dysfunction in these 
      animals, it has no effect on either glucose-induced insulin secretion or insulin 
      sensitivity. These observations suggest that FGF1 acts in the brain to stimulate 
      insulin-independent glucose clearance. On the basis of our finding that icv FGF1 
      treatment increases hepatic glucokinase gene expression, we considered the 
      possibility that increased hepatic glucose uptake (HGU) contributes to the 
      insulin-independent glucose-lowering effect of icv FGF1. Consistent with this 
      possibility, we report that icv FGF1 injection increases liver glucokinase 
      activity by approximately twofold. We conclude that sustained remission of 
      hyperglycemia induced by the central action of FGF1 involves both preservation of 
      beta-cell function and stimulation of HGU through increased hepatic glucokinase 
      activity.
CI  - (c) 2018 by the American Diabetes Association.
FAU - Scarlett, Jarrad M
AU  - Scarlett JM
AUID- ORCID: 0000-0003-1019-346X
AD  - University of Washington Medicine Diabetes Institute, Department of Medicine, 
      University of Washington, Seattle, WA.
AD  - Gastroenterology and Hepatology, Department of Pediatrics, University of 
      Washington, Seattle, WA.
FAU - Muta, Kenjiro
AU  - Muta K
AD  - University of Washington Medicine Diabetes Institute, Department of Medicine, 
      University of Washington, Seattle, WA.
FAU - Brown, Jenny M
AU  - Brown JM
AD  - University of Washington Medicine Diabetes Institute, Department of Medicine, 
      University of Washington, Seattle, WA.
FAU - Rojas, Jennifer M
AU  - Rojas JM
AD  - University of Washington Medicine Diabetes Institute, Department of Medicine, 
      University of Washington, Seattle, WA.
AD  - Department of Physiology, Institute for Diabetes, Obesity and Metabolism, 
      Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
FAU - Matsen, Miles E
AU  - Matsen ME
AD  - University of Washington Medicine Diabetes Institute, Department of Medicine, 
      University of Washington, Seattle, WA.
FAU - Acharya, Nikhil K
AU  - Acharya NK
AD  - University of Washington Medicine Diabetes Institute, Department of Medicine, 
      University of Washington, Seattle, WA.
FAU - Secher, Anna
AU  - Secher A
AD  - Novo Nordisk A/S, Malov, Denmark.
FAU - Ingvorsen, Camilla
AU  - Ingvorsen C
AD  - Novo Nordisk A/S, Malov, Denmark.
FAU - Jorgensen, Rasmus
AU  - Jorgensen R
AD  - Novo Nordisk A/S, Malov, Denmark.
FAU - Hoeg-Jensen, Thomas
AU  - Hoeg-Jensen T
AD  - Novo Nordisk A/S, Malov, Denmark.
FAU - Stefanovski, Darko
AU  - Stefanovski D
AD  - New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, 
      Philadelphia, PA.
FAU - Bergman, Richard N
AU  - Bergman RN
AUID- ORCID: 0000-0003-1539-4471
AD  - Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los 
      Angeles, CA.
FAU - Piccinini, Francesca
AU  - Piccinini F
AD  - Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los 
      Angeles, CA.
FAU - Kaiyala, Karl J
AU  - Kaiyala KJ
AD  - Department of Oral Health Sciences, School of Dentistry, University of 
      Washington, Seattle, WA.
FAU - Shiota, Masakazu
AU  - Shiota M
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University School 
      of Medicine, Nashville, TN.
FAU - Morton, Gregory J
AU  - Morton GJ
AUID- ORCID: 0000-0002-8106-8386
AD  - University of Washington Medicine Diabetes Institute, Department of Medicine, 
      University of Washington, Seattle, WA.
FAU - Schwartz, Michael W
AU  - Schwartz MW
AUID- ORCID: 0000-0003-1619-0331
AD  - University of Washington Medicine Diabetes Institute, Department of Medicine, 
      University of Washington, Seattle, WA mschwart@u.washington.edu.
LA  - eng
GR  - T32 HL007028/HL/NHLBI NIH HHS/United States
GR  - T32 DK007247/DK/NIDDK NIH HHS/United States
GR  - R01 DK083042/DK/NIDDK NIH HHS/United States
GR  - R01 DK029867/DK/NIDDK NIH HHS/United States
GR  - P30 DK035816/DK/NIDDK NIH HHS/United States
GR  - R01 DK101997/DK/NIDDK NIH HHS/United States
GR  - R01 DK027619/DK/NIDDK NIH HHS/United States
GR  - P30 DK017047/DK/NIDDK NIH HHS/United States
GR  - T32 HL007312/HL/NHLBI NIH HHS/United States
GR  - R01 DK089056/DK/NIDDK NIH HHS/United States
GR  - K08 DK114474/DK/NIDDK NIH HHS/United States
GR  - R37 DK027619/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20181206
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 104781-85-3 (Fibroblast Growth Factor 1)
RN  - EC 2.7.1.2 (Glucokinase)
CIN - Nat Rev Endocrinol. 2019 Feb;15(2):66. PMID: 30573763
CIN - Diabetes. 2019 Mar;68(3):476-478. PMID: 30787069
MH  - Animals
MH  - Blood Glucose/drug effects
MH  - Diabetes Mellitus, Experimental/drug therapy/metabolism
MH  - Diabetes Mellitus, Type 2/drug therapy/metabolism
MH  - Fibroblast Growth Factor 1/*therapeutic use
MH  - Glucokinase/genetics/metabolism
MH  - Glucose Tolerance Test
MH  - Humans
MH  - Hypoglycemic Agents/therapeutic use
MH  - Insulin/metabolism
MH  - Insulin Resistance
MH  - Male
MH  - Rats
MH  - Rats, Zucker
MH  - Real-Time Polymerase Chain Reaction
PMC - PMC6385755
EDAT- 2018/12/14 06:00
MHDA- 2019/08/27 06:00
PMCR- 2020/03/01
CRDT- 2018/12/08 06:00
PHST- 2018/05/03 00:00 [received]
PHST- 2018/10/29 00:00 [accepted]
PHST- 2018/12/14 06:00 [pubmed]
PHST- 2019/08/27 06:00 [medline]
PHST- 2018/12/08 06:00 [entrez]
PHST- 2020/03/01 00:00 [pmc-release]
AID - db18-0498 [pii]
AID - 0498 [pii]
AID - 10.2337/db18-0498 [doi]
PST - ppublish
SO  - Diabetes. 2019 Mar;68(3):654-664. doi: 10.2337/db18-0498. Epub 2018 Dec 6.