To understand better impairment of glucose utilization in diabetics during a hyperosmolal state, in vitro models were established to evaluate the effects of hyperosmolality on basal glucose uptake as well as glucagon dependent glucose release by isolated hepatocytes. In these studies simulating a hyperglycaemic (40 mmol glucose) and hyperosmolal (up to 500 mosm kg-1, NaCl as added solute) state basal hepatic glucose uptake was reversibly suppressed by 19% when osmolality was increased by as little as 10 mosm kg-1. No such effects on glucose uptake by isolated hepatocytes could be attained when the incubation's fluid osmolality was augmented by the addition of urea or mannitol. Estimations of the transport rates of 3-O-methylglucose and uptake of 2-deoxyglucose at 400 vs. 300 mosm kg-1 revealed that impaired intracellular enzymatic activity but not the transport rate of glucose into the cell were responsible for the hyperosmolal defect as uptake was more reduced (P less than 0.025) by increased osmolality for 2-deoxyglucose (16%) than for 3-O-methylglucose (13%). Glucagon dependent glucose release from isolated hepatocytes was diminished by 17.8% when the osmolality was raised to 400 mosm kg-1 by NaCl as added solute. These data obtained in vitro support the clinical contention that a hyperosmolal state, which corresponds to a loss of fluid in excess of solutes, is able to impair basal hepatic glucose uptake as well as glycogenolytic glucagon action on the liver.

No abstract

This preliminary study was designed to determine whether biologic action of biosynthetic human insulin (BHI) in vitro and its antigenicity in man equals that of various insulins of pancreatic origin. Testing the biologic action of BHI, pancreatic human insulin (PHI), and pancreatic pork insulin (PCPI) on glucose uptake by the rat hemidiaphragm and adipose tissue, identical efficacy for the insulins on a unit per unit basis was observed. Furthermore, a comparable impairment of insulin action was seen under the detrimental conditions of a hyperosmolal state. In an insulin-dependent diabetic female patient with cutaneous insulin hypersensitivity, BHI displayed the same antigenicity as PHI and PCPI. From these data we conclude tht BHI, both in vitro and in vivo, exhibits the same biologic properties as pancreatic insulin, and that it is reasonable to continue extensive testing of BHI in man, since identical metabolic effects and immunologic reactions are to be anticipated as with purified pancreatic insulin preparations of human or animal origin.

No abstract

No abstract