Studies on the Biologic Actions of Biosynthetic Human Insulin In Vitro and in Diabetic Man

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.

Human Insulin

“…However, extension of lipoatrophy in I patient apparently due to semisynthetic human insulin was reported by Rosman (1986). Since cross-reactivity between human insulin and pancreatic insulin of animal origin has been reported, it is to be expected that some patients with local or systemic allergy to pork and/or beef insulins will also exhibit allergy to biosynthetic human insulin as reported by Gossain et al (\ 984), Grammer et al (\ 984), Small and Lerman (\ 984), Waldhausl et al (1981) and Wiles et al (\983) or to semisynthetic (Altman et al 1983;Blandford et al 1982;Bruni et al 1983;Carveth-lohnson et al 1982;Kristensen & Falholt 1983), or to both (Schernthaner et al 1981). There have been reports of a new allergic reaction to semisynthetic human insulin (Silverstone 1986) and to biosynthetic insulin (Grammer et al 1987) in patients wlthout previous reaction to porcine or bovine insulin.…”

Effect of hyperosmolality on basal and hormone‐stimulated hepatic glucose metabolism in vitro

“…Hyperosmolality induced by NaCl, LiC1, mannitol or choline chloride has been reported to reversibly stimulate glucose uptake and metabolism by rat epididymal fat pads, isolated fat cells, muscle and hemidiaphragms [8,[10][11][12][13]201. Furthermore, it has been shown by 3-0methylglucose uptake studies that hyperosmolality mimics insulin action in causing a rapid acceleration of carrier-mediated glucose transport across cell membranes of rat epididymal fat pad and muscle [9].…”

“…In contrast, in vitro studies on the effect of hyperosmolality on insulin-mediated sugar transport and metabolism revealed that total glucose uptake by rat muscle and adipose tissue remained unchanged. Correcting, however, for the hyperosmolality-induced rise in basal insulin independent glucose uptake deterioration by hyperosmolality of insulin-stimulated glucose uptake and utilization became apparent [8,10,12]. Similarly, a net decrease in xylose uptake was observed in insulin-treated soleus muscles [13].…”