The impact of prolonged hyperinsulinaemia on glucose transport in equine skeletal muscle and digital lamellae
de Laat MA, Clement CK, Sillence MN, McGowan CM, Pollitt CC, Lacombe VA
"REASONS FOR PERFORMING STUDY:An increased incidence of metabolic disease in horses has led to heightened recognition of the pathological consequences of insulin resistance (IR). Laminitis, failure of the weight-bearing digital lamellae, is an important consequence. Altered trafficking of specialised glucose transporters (GLUTs) responsible for glucose uptake, are central to the dysregulation of glucose metabolism and may play a role in laminitis pathophysiology.
OBJECTIVES:We hypothesised that prolonged hyperinsulinaemia alters the regulation of glucose transport in insulin-sensitive tissue and digital lamellae. Our objectives were to compare the relative protein expression of major GLUT isoforms in striated muscle and digital lamellae in healthy horses and during hyperinsulinaemia.
STUDY DESIGN:Randomised, controlled study.
METHODS:Prolonged hyperinsulinaemia and lamellar damage were induced by a prolonged-euglycaemic hyperinsulinaemic clamp (p-EHC) or a prolonged-glucose infusion (p-GI) and results were compared to electrolyte-treated controls. GLUT protein expression was examined with immunoblotting.
RESULTS:Lamellar tissue contained more GLUT1 protein than skeletal muscle (p = 0.002) and less GLUT4 than the heart (p = 0.037). During marked hyperinsulinaemia and acute laminitis (induced by the p-EHC), GLUT1 protein expression was decreased in skeletal muscle (p = 0.029) but unchanged in the lamellae, while novel GLUTs (8; 12) were increased in the lamellae (p = 0.03), but not skeletal muscle. However, moderate hyperinsulinaemia and subclinical laminitis (induced by the p-GI) did not cause differential GLUT protein expression in the lamellae vs. control horses.
CONCLUSIONS:The results suggest that lamellar tissue functions independently of insulin and that IR may not be an essential component of laminitis aetiology. Marked differences in GLUT expression exist between insulin-sensitive and insulin-independent tissues during metabolic dysfunction in horses. The different expression profiles of novel GLUTs during acute and subclinical laminitis may be important to disease pathophysiology and require further investigation."
This research should be read in conjunction with
de Laat M, Sillence M, McGowan C, Pollitt C
Insulin-Induced Laminitis - An investigation of the disease mechanism in horses
RIRDC Dec 2011
Chapter 5. Glucose uptake in the hoof is largely facilitated by insulin-independent GLUT-1 glucose transporters.
Asplin KE, Curlewis JD, McGowan CM, Pollitt CC, Sillence MN
Glucose transport in the equine hoof
Equine vet. J. (2011) 43 (2) 196-201