Relationships between the structure of insulin and its physiological effects - Thyronine insulin analogues

TY - CHAP

T1 - Relationships between the structure of insulin and its physiological effects - Thyronine insulin analogues

AU - Dieken, M L

AU - Federwisch, M

A2 - DeMeyts, P

PY - 2002

Y1 - 2002

N2 - Elucidation of the structure of insulin has provided opportunities to explain its physiological properties. Following secretion directly into the hepatic portal vein, which flows directly to the liver, it acts initially to modulate hepatic glucose output, an effect primarily responsible for glucose homeostasis. Only 50% of secreted insulin passes from the liver to the other tissues where it has a role in controlling lipolysis and glucose uptake particularly after meals. In evolutionary terms selection pressure may have acted to optimize the affinity of the insulin to insulin receptor interaction in order to define the most appropriate relative hepatic to peripheral ratio of insulin action. Therapeutically insulin is given subcutaneously. This unphysiological route results in relative under-exposure of the liver to insulin with peripheral hyperinsulinaemia. By exploiting the peripheral capillary endothelium as a molecular sieve it is proving possible to design insulin analogues which compensate for this imbalance.

AB - Elucidation of the structure of insulin has provided opportunities to explain its physiological properties. Following secretion directly into the hepatic portal vein, which flows directly to the liver, it acts initially to modulate hepatic glucose output, an effect primarily responsible for glucose homeostasis. Only 50% of secreted insulin passes from the liver to the other tissues where it has a role in controlling lipolysis and glucose uptake particularly after meals. In evolutionary terms selection pressure may have acted to optimize the affinity of the insulin to insulin receptor interaction in order to define the most appropriate relative hepatic to peripheral ratio of insulin action. Therapeutically insulin is given subcutaneously. This unphysiological route results in relative under-exposure of the liver to insulin with peripheral hyperinsulinaemia. By exploiting the peripheral capillary endothelium as a molecular sieve it is proving possible to design insulin analogues which compensate for this imbalance.

M3 - Conference paper

SN - 1-4020-0655-1

SP - 121

EP - 130

BT - Unknown

PB - KLUWER ACADEMIC PUBL

CY - DORDRECHT

T2 - Alcuin Symposium on Insulin and Related Proteins

Y2 - 1 January 2002

ER -