title: Elevated nocturnal NEFA are an early signal for hyperinsulinaemic compensation during diet-induced insulin resistance in dogs.
abstract: OBJECTIVE
  A normal consequence of increased energy intake and insulin resistance is compensatory hyperinsulinaemia through increased insulin secretion and/or reduced insulin clearance. Failure of compensatory mechanisms plays a central role in the pathogenesis of type 2 diabetes mellitus; consequently, it is critical to identify in vivo signal(s) involved in hyperinsulinaemic compensation. We have previously reported that high-fat feeding leads to an increase in nocturnal NEFA concentration. We therefore designed this study to test the hypothesis that elevated nocturnal NEFA are an early signal for hyperinsulinaemic compensation for insulin resistance.
  
  
  METHODS
  Blood sampling was conducted in male dogs to determine 24 h profiles of NEFA at baseline and during high-fat feeding with and without acute nocturnal NEFA suppression using a partial A1 adenosine receptor agonist.
  
  
  RESULTS
  High-fat feeding increased nocturnal NEFA and reduced insulin sensitivity, effects countered by an increase in acute insulin response to glucose (AIR(g)). Pharmacological NEFA inhibition after 8 weeks of high-fat feeding lowered NEFA to baseline levels and reduced AIR(g) with no effect on insulin sensitivity. A significant relationship emerged between nocturnal NEFA levels and AIR(g). This relationship indicates that the hyperinsulinaemic compensation induced in response to high-fat feeding was prevented when the nocturnal NEFA pattern was returned to baseline.
  
  
  CONCLUSIONS
  Elevated nocturnal NEFA are an important signal for hyperinsulinaemic compensation during diet-induced insulin resistance.
authors.affiliation: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA. josianebroussard@gmail.com.
authors.forename: Josiane L
authors.initials: JL
authors.lastname: Broussard
authors.affiliation: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
authors.forename: Cathryn M
authors.initials: CM
authors.lastname: Kolka
authors.affiliation: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
authors.forename: Ana V B
authors.initials: AV
authors.lastname: Castro
authors.affiliation: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Asare Bediako
authors.affiliation: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Paszkiewicz
authors.affiliation: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Szczepaniak
authors.affiliation: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
authors.forename: Lidia S
authors.initials: LS
authors.lastname: Szczepaniak
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Knutson
authors.affiliation: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
authors.forename: Stella P
authors.initials: SP
authors.lastname: Kim
authors.affiliation: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Bergman
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose; D002940:Circadian Rhythm / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000662:veterinary*; D004032:Diet; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D006946:Hyperinsulinism / Q000097:blood / Q000175:diagnosis / Q000662:veterinary*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D008297:Male
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin
keywords: Disposition index; Glucose tolerance; Insulin compensation; Non-esterified fatty acids; Type 2 diabetes