Studies on diabetic beta-1 lipoprotein

Abstract

We prepared β1-lipoprotein from human diabetic serum and studied its diabetogenic action. The Following results were obtained.1) Intravenously injected insulin I131 was retained in the blood of diabetic patients with and without insulin treatment.Therefore, it was suggested that diabetics had common unknown extracellular factors in their serum which impeded the distribution of insulin I131 to the tissue. At the same time, the blood sugar reduction by insulin was lower in diabetics than in normals.2) Diabetic β1-lipoprotein inhibited the glucose output of rat liver-slices and the glucose uptake of rat diaphragms, but in normal ones it accelerated both.3) Diabetic β1-lipoprotein inhibited the binding of insulin I131 to liver, kidney and muscle slices of rats. Consequently it was suggested that the retardative factors of insulin I131 in blood might be diabetic β1-lipoprotein.4) Diabetic β1-lipoprotein intravenously injected, was more distributed than normal to target organs, and the blood concentration of the former was lower than that of the latter. These findings were in contrast with the concentration curve of insulin I131 (mentioned in 1).At this experiment, after an injection of diabetic β1-lipoprotein the blood sugar increased but decreased after normal.5) The greatest amount of injected diabetic β1-lipoprotein I131 distributed to cell membrane and was not washed out by diffusion.Therefore, chemical binding of lipoprotein with cell membrane was thought to be the reason.6) According to the above mentioned findings, it was thought that, Diabetic β1-lipoprotein intravenously injected, rapidly bound with cell membranes of target organs of insulin and thus inhibited the active transport of glucose of insulin and elevated the blood sugar level.7) By an intravenous injection of diabetic β1-lipoprotein blood sugar was slowly increased and reached its maximum after 4 hours of injection and after 6 hours hyperglycemia still continued. By daily injection, continuous hyperglycemia was obtained.The mechanism of hyperglycemia was thought due to the inhibition of peripheral glucose utilization.8) An intravenous injection of diabetic β1-lipoprotein inhibited the action of insulin and elevated the blood sugar level.9) By the use of infrared-spectrophotometry, it was observed that diabetic β1-lipoprotein did not contain any unknown substance and the proportion of chemical composition of its fraction was not abnormal.10) As the result of chemical analysis of diabetic β1-lipoprotein, cholesterol, phospholipid, neutral fat and protein were slightly larger in quantity than normal.11) By the use of metachromasy of methylorange it was made clear, that the protein fraction of diabetic β1-lipoprotein was different from normal.Therefore the structure of protein of diabetic β1-lipoprotein seemed to be abnormal.