Restoration of Glucose Homeostasis in Insulin-dependent Diabetic Subjects: An Inducible Process

Abstract

To assess the change in glucose handling capability of diabetic patients regulated with an artificial beta-cell, five insulin-dependent diabetic subjects were challenged with a 100-g glucose meal while on conventional (*single or split mixed insulin injections) therapy and again after 72 h on an artificial beta-cell unit. It was determined that while receiving conventional therapy, the diabetic patient's capacity to oxidize glucose was severely impaired. In addition, glucose storage was markedly reduced. After 72 h on the artificial beta-cell unit, the diabetic patient's capacity to oxidize glucose following the ingestion of the glucose meal significantly exceeded that of the control group, and glucose storage returned to normal. Since the above study did not reveal the amount of time on the artificial beta-cell required to restore the glucose processing capability of the diabetic patients to normal, their response to a mixed test meal ingested at noon was monitored while they were on conventional insulin therapy and during four consecutive days that they were on the artificial beta-cell. This inquiry revealed a gradual increase in their capacity to oxidize carbohydrate in response to the test meal. In contrast, their ability to store carbohydrate was normalized within 24 h following initiation of artificial beta-cell therapy. These studies clearly reveal that the conventionally treated diabetic patient's capacity to both oxidize and store carbohydrate is severely impaired. Both functions can be restored to normal by the use of the artificial beta-cell for 48-72 h. Most importantly, the gradual improvement in carbohydrate oxidation with respect to the daily mixed meal challenge suggests that it is an "inducible" process which requires at least 2-3 days to accomplish. Since the ability to both oxidize and store incoming carbohydrate is essential for glucose homeostasis, these observations may have significant implications for the care of diabetic patients.

Effects of Basal Insulin Supplementation on Disposition of Mixed Meal in Obese Patients With NIDDM

“…Of interest, although preprandial injection of soluble insulin did not stimulate overall glucose uptake, it significantly increased postprandial glucose oxidation, implying an alteration in the intracellular pathway of metabolism. The latter result is reminiscent of the report by Foss et al (73) that intravenous soluble insulin increased glucose oxidation after ingestion of a mixed meal in patients with insulin-dependent diabetes mellitus.…”

Chronic Intermittent Intravenous Insulin Therapy: A New Frontier in Diabetes Therapy

“…After glucose administration, CO 2 production (and consequently the RQ) increases (0.9-1.0), indicating that glucose has become the primary source of energy. In contrast, in the patient with diabetes mellitus on conventional insulin therapy, no such increase in RQ 21,22 or CO 2 production 23 is observed. The possible fate of ingested glucose is (a) oxidation (liver, brain, muscle), (b) conversion to fat (liver, muscle, adipose tissue), (c) storage as glycogen (liver, muscle) or transamination of intermediary metabolites to form amino acids (e.g., alanine).…”

Role of Muscle in CO2 Production After Oral Glucose Administration in Man

“…However, this ability to oxidize dietary carbohydrate can be restored to normal with near-physiologic, artificial beta cell-directed insulin therapy. 2 …”

“…In contrast, in type I diabetic subjects on conventional insulin therapy, no such increase in RQ 12 or CO 2 production (unpublished observations) is observed. The possible metabolic sequelae of glucose after the ingestion of 100 g of this fuel are (1) oxidation (liver, muscle, brain), (2) conversion to fat (liver, muscle, adipose tissue), (3) storage as glycogen (liver, muscle), and (4) transamination of intermediary products of glucose utilization to form amino acids (e.g., alanine). While the first two metabolic pathways are associated with an increase in RQ, the last two are not.…”