Tissue-specific differences in insulin binding affinity and insulin receptor concentrations in skeletal muscles, adipose tissue depots and liver of cattle and sheep

Abstract

Differences in insulin binding affinity and in concentrations of insulin receptor, were found in a variety of tissues taken, at slaughter, from mature steers (701 (s.d. 23) kg) and growing lambs (47 (s.d. 2·1) kg). In both species, liver had lower insulin binding affinity than skeletal muscles m. pectineus m. longissimus dorsi and m. rectus capitis (all P < 0·001) and subcutaneous, omental and perirenal adipose depots (all P < 0·001). Site-specific differences in affinity for insulin existed between adipose depots (subcutaneous < omental, P < 0·05; subcutaneous < perirenal, P < 0·001) and between tissue-types (subcutaneous fat < m. pectineus skeletal muscle, P < 0·05; m. rectus capitis < perirenal fat, P < 0·05) in steers. In lambs also, receptor affinity for insulin differed between tissue-type (m. longissimus dorsi < perirenal fat, P < 0·05; m. rectus capitis < subcutaneous fat, P < 0·05 and m. rectus capitis < perirenal fat, P < 0·001) but lambs did not show the adipose depot-specific differences in insulin affinity observed in steers. Insulin receptor concentration differed between adipose depots (subcutaneous < omental, P < 0·05; subcutaneous < perirenal, P < 0·01) and between tissue-type (m. pectineus < perirenal fat P < 0·05) in steers and perirenal and subcutaneous adipose depots of lambs had higher receptor concentrations than m. longissimus dorsi and m. pectineusP < 0·001). This is the first study to demonstrate, in any species, differences in insulin receptor binding affinity and receptor concentration in a wide range of tissues (liver, skeletal muscles and adipose depots) from the same individual. Such differences in meat-producing animals could, through effects on tissue sensitivity and/or responsiveness to insulin, influence nutrient partitioning to tissues and affect overall rates of lipid storage and net protein synthesis.

A partial cDNA sequence of the ovine insulin receptor gene: evidence for alternative splicing of an exon 11 region and for tissue-specific regulation of receptor isoform expression in sheep muscle, adipose tissue and liver

“…Previous demonstrations of differences in insulin binding affinity between muscle and adipose depots of cattleand of sheep in our laboratory (McGrattan et al 1997, Wylie et al 1998) and of differences in the insulin binding affinity of the human A and B alternatively spliced insulin receptor isoforms when expressed in cultured cell lines (Mosthaf et al 1990), combined with indications of tissue-specific expression of the human and rat A and B isoforms (Seino & Bell 1989, Mosthaf et al 1990, suggest that alternative splicing of the insulin receptor may be one mechanism by which the responsiveness of insulinsensitive tissues to insulin is modulated in ruminant and non-ruminant animals. Alteration of the ratio of expressed receptor isoforms and, hence, the overall affinity of individual tissues for insulin may influence the way in which nutrients are partitioned to, and ultimately utilised by, competing tissues (e.g.…”

“…The actual physiological significance of this difference in expression of the two alternatively spliced receptor isoforms and in insulin binding affinity between liver and other tissues in ruminants (McGrattan et al 1997, Wylie et al 1998) is unknown, but it is considered significant that liver is exposed to portal insulin concentrations which are typically 2-to 3-fold higher than peripheral insulin concentrations. The predominance of the lower affinity exon 11 + insulin receptor transcript in liver is consistent with the lower overall insulin binding affinity of this tissue in both cattle (McGrattan et al 1997) and sheep (Wylie et al 1998) and may allow liver to respond appropriately to fluctuating, and occasionally high, portal insulin concentrations while accommodating and permitting insulin's metabolic effects and providing significant hepatic clearance of insulin.…”

“…The affinity of the insulin receptor for insulin has been shown by classical hormone-binding studies to differ between pig breeds (Camara & Mourot 1996) and between tissues in humans (Bolinder et al 1983, Kotzke et al 1995 and in the ruminant (McGrattan et al 1997, Wylie et al 1998. Differences in insulin binding affinity (K d ) between liver, muscle and fat of sheep (Wylie et al 1998) may underlie altered tissue responsiveness to insulin, but it is unclear how or why differences in insulin binding affinity between tissues arise.…”

Insulin Signaling in Liver and Adipose Tissues in Periparturient Dairy Cows Supplemented with Dietary Nicotinic Acid

“…However, the physiological role of this local effect in RPAT for systemic insulin sensitivity is unclear. A tissue-specific regulation of insulin responsiveness in cattle was also discussed by McGrattan et al [ 19 ] who demonstrated that insulin receptor concentration in subcutaneous adipose tissue was lower than that in omental adipose tissue in steers.…”

Ryegrass-based diet and barley supplementation: Partition of energy-yielding nutrients among splanchnic tissues and hind limbs in finishing lambs1

“…Grain supplementation is known to modify carcass composition of grazing ruminants toward a greater adiposity (Murphy et al, 1994) as a result of an increase in the level of intake (Smith et al, 1992;Greathead et al, 2001) and an alteration in the profile of nutrients available to peripheral tissues (Scollan and Jessop, 1995). McGrattan et al (2000) reported a higher receptor affinity for insulin in adipose tissues than in the muscle of lambs, which is coherent with an increase in the uptake of energy-yielding nutrients by peripheral adipose tissues other than those included in the hind limbs. These results should be confirmed with a higher number of animals.…”