The study was concerned with the comparison of the action profile of regular and NPH preparations of human insulin (recombinant DNA) and of PPI (pork purified insulin). In addition, the action profiles of some mixtures (10:90, 15:85, 20:80, 25:75, 30:70) of regular and NPH human insulin were evaluated. The comparisons were based on the Gerritzen test. There was no statistically significant difference in the time-course of the blood glucose levels after administration of NPH human insulin and NPH PPI. A tendency was noted, however, that NPH human insulin has a faster onset of action and that the serum glucose minimum for NPH human insulin lasts longer. The serum glucose curves after the application of regular and NPH human insulin initially lie closer together than after the respective PPI preparations. In the later phase, regular human insulin interferes less with the NPH curves. This means that combinations of regular and NPH human insulin may have a clinically useful action profile. No skin reaction or other adverse reaction was detected after application of human insulin and no antibodies against human insulin and Escherichia coli protein were found.
After a short term oral administration of 25 mg buformin per animal (100--125 mg/kg/day) and final intraperitoneal injection of glucose we found a significantly increased content of glycogen in the diaphragm of normal male and female rats together with a higher incorporation of glucose. The latter effect was not observed if the last dose of buformin was given 24 h before the investigation. No effect on glycogen content or glucose incorporation into the glycogen was measurable after daily administration of 2.5 mg buformin per animal for 14 days or a single dose of 25 mg buformin per animal.The present investigation confirms the clinical experience that the effect of biguanides is seen only after some days of treatment.
Biosynthetic human insulin (BHI) produced by recombinant DNA technology has been proven to be identical to pancreatic human insulin. It differs from pork insulin in one carboxy-terminal amino acid of the B-chain, where alanine substitutes for threonine. This leads to a higher hydrophilicity and usually lowers the tendency of insulin molecules to aggregate. To study its biologic effect in man, the Gerritzen test was applied. BHI regular (10 IU) or purified pork insulin (PPI) (10 IU) was injected subcutaneously to evaluate the insulin action profile. The time course of plasma glucose levels under both BHI and PPI did not differ significantly. BHI seems to lower the blood glucose somewhat faster during the first 30 min and, during the late phase, somewhat less than pork insulin. In general, for both BHI and PPI, the onset of action occurs within 15 and 30 min; after 60 min, plasma glucose levels drop by 44.3% for BHI and by 40% for PPI. The plasma glucose minimum was reached about 2 h after injection; therefore, the slope of the plasma glucose fall after 60 min was only marginal. The minimum levels were steady over about 1.75 h. At 2.5 h postinjection plasma glucose rose gradually and reached starting levels after about 7 h. BHI was as well tolerated in the intradermal skin testing as were pork insulin and a placebo solution, DIABETES CARE 4: 180-182, MARCH-APRIL 1981.
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