The insulin receptor binding of human and pork insulin was measured in four different pork brain tissues. In medial hypothalamus, infundibulum of pituitary gland, neurohypophysis, and adenohypophysis insulin receptors were found. Binding of mono-125I-(TyrA14)-insulin proceeded rapidly at 37 degrees C, pH 7.4, and reached a steady state for human and pork insulin at 15 minutes. Biosynthetic human insulin and semisynthetic human insulin dissociated more rapidly than pork insulin. In the four tested brain tissues the specific insulin binding per mg protein differed significantly (2p less than 0.01). The receptor affinity constant of human insulin was significantly (2p less than 0.01) lower in comparison to pork insulin in the four brain tissues studied. This study demonstrates that there are insulin receptors in pork brain tissue, that the amounts of these receptors vary depending on the area and that the brain insulin receptors react differently to pork and human insulin.

The glucose clamp technique was used to compare the biological activity of purified porcine insulin and Biosynthetic Human Insulin (BHI). An intravenous bolus of 0.1 U/kg BW was injected in eight male volunteers, and the glucose was clamped at baseline values (euglycemic clamp). Serum insulin, serum C-peptide and plasma glucose did not differ between porcine and human insulin. The insulin induced glucose consumption differed significantly (p less than 0.007) between purified porcine insulin (50.5 +/- 5.2 [SEM] g/2h) and Biosynthetic Human Insulin (63.5 +/- 4.5 g/2h). Purified porcine insulin induced a hormonal response with significantly (p less than 0.05) elevated concentrations of serum growth hormone (12.1 +/- 0.25 ng/ml) and serum cortisol (161.4 +/- 28.6 ng/ml), which were not observed following Biosynthetic Human Insulin (serum growth hormone: 2.6 +/- 0.2 ng/ml; serum cortisol: 117.3 +/- 14.8 ng/ml). The data confirm earlier results indicating hormonal and metabolic differences between human and porcine insulin.

The biologic effect of human insulin (recombinant DNA) and purified pork insulin (PPI) was compared during insulin-induced hypoglycemia at two intravenous dosages 0.075 and 0.1 U/kg body wt in 12 healthy volunteers. Serum insulin concentrations and plasma glucose curves were identical. PPI induced a significantly (P < 0.05) higher output of epinephrine, growth hormone, and cortisol at both doses. Less inhibition (P < 0.05) of endogenous insulin secretion was observed for human insulin at 0.1 U/kg body wt. An elevated incidence of sweating during hypoglycemia was related to epinephrine secretion. The results indicate that homologous insulin produces in vivo effects which are different from those produced by heterologous insulin.

Human insulin (recombinant DNA) and purified pork insulin (PPI) were administered intravenously at a dosage of 0.075 U/kg in eight healthy men. Both insulins exerted the same hypoglycemic effect with the same restoration pattern to normal glucose levels at the end of the test. Differences were found with respect to a stronger antilipolytic and antiketogenic effect of human insulin; also the reactive rise of both compounds at the end of the test is less under human insulin in comparison with PPI. In spite of the same glucose nadir, the pattern of hormonal counterregulation is different under human insulin in comparison with PPI. There was less epinephrine and glucagon and practically no prolactin secretion following human insulin. Growth hormone secretion is augmented under human insulin. The clinical significance of these results under long-term treatment with human insulin has to be assessed.

In two double-blind studies 66 insulin-dependent diabetic subjects pretreated with pork insulin were changed to human insulin (recombinant DNA) or a purified pork insulin preparation (regular and NPH insulin). Sixty-five patients previously pretreated with beef insulin were transferred, in a randomized, double-blind fashion, to human insulin and purified beef insulin of the same preparations (regular and NPH insulin). Patients’ metabolic control, as demonstrated by fasting and 1-h postprandial blood glucose, HbA1c, and daily insulin dosage, over 4 mo was unchanged in our four groups compared with the values before changing insulin preparation. No severe hypoglycemic attacks or skin reactions were reported.

This study investigates and compares human insulin (recombinant DNA) and purified porcine insulin (PPI) in healthy volunteers and in type II diabetic patients, in terms of whether both these insulins were capable of influencing in a different manner pancreatic glucagon, C-peptide, and free fatty acids (FFA) concentrations. The findings reveal that the beta-cell of human pancreas apparently recognizes human insulin more readily than PPI, as assessed by the inhibition of C-peptide, and a similar conclusion follows for the alpha-cell; this conclusion is underscored by the inhibited glucagon values. The delayed increments of glucagon under human insulin following arginine stimulation may be the result of a more rapid insulin absorption from subcutaneous tissue and a greater biologic action of this insulin in comparison with the PPI. Finally, human insulin has additional properties as demonstrated by its stronger antilipolytic effects.