Yoshikazu Goriya

Glycaemic Control in Pancreatectomized Dogs with a Wearable Artificial Endocrine Pancreas

SummaryA needle-type glucose sensor has been developed using a platinum electrode covered with immobilized glucose oxidase. Experiments with albumin-saline solution in vitro showed that at 5.5 mmol/l glucose concentration the output current generated was 1.2±0.4 nA (mean ± SD). The current increased as a linear function of glucose concentration over the range (0–27.7 mmol/l). The response time to reach 90% of the final plateau value was 16.2±6.2 s. The signal-to-noise ratio of the sensor was 15.8±2.6 decibels. The temperature coefficient in output was 2.3±1.0%/°C. The current output was not affected significantly by changes in oxygen tension of the solution in the range 25–150 mmHg.In vivo, the output current of sensors inserted into the subcutaneous tissues of dogs was directly related to blood glucose concentrations after oral glucose or meals. Daily checking of the sensors maintained in subcutaneous tissues in five dogs showed that the sensitivity decreased gradually to 87.2±7.6% at 72 h, and dropped significantly to 57.4±7.0% of the initial output by 96 h.A wearable artificial endocrine pancreas (18.0 × 17.7 × 7.9 cm, 700 g) was developed, consisting of a needle-type glucose sensor, a microcomputer system and a pump driving mechanism. Three pancreatectomized dogs were fitted with the system by inserting the sensor into subcutaneous tissue. By renewing the sensor every fourth day, the device could maintain the daily glucose variations in diabetic dogs within the range 5–9.5 mmol/l for 7 days.

Increased intestinal absorption of insulin in a micellar solution: Water-in-oil-in-water insulin micelles

SummaryWater-in-oil-in-water (W/O/W) insulin micelles were prepared, and the possibility of insulin absorption in a micellar form was examined. In this preparation, insulin was trapped in oil droplets of oleic acid in glyceryl-α-monooleate. (1) W/O/W insulin micelles were absorbed from the ligated jejunal loop of rabbits to the order of 12.3 to 58.5% of the dose given (10 U/kg body weight) during the 3-h experimental period. (2) Alloxan diabetic rats were treated with intrajejunal administration of W/O/W insulin micelles at a dosage of either 25 or 50 U/100 g body weight, three times daily for as longs as 14 days. During treatment, a significant reduction in the daily excretion of urinary glucose was observed, concomitant with a decrease in fasting blood glucose. Quantitative estimates suggested that the effectiveness of 25 U/100 g of intrajejunal W/O/W insulin micelles was comparable to that of regular insulin at a dosage of 1 U/100 g i.m. These results would indicate that W/O/W insulin micelles, when given enterally, are more effective in lowering blood and urinary glucose levels than W/O/W insulin emulsions in which insulin was trapped in oil droplets of triglyceride.

Improvement in blunted glucagon response to insulin-induced hypoglycemia by strict glycemic control in diabetics

To elucidate the mechanism of impaired pancreatic A cell function in hypoglycemia in diabetics, the effect of long-term strict glycemic regulations on hypoglycemia-induced glucagon secretion was studied. Firstly, the effect of plasma insulin concentrations on suppressing A cell was studied in healthy volunteers by injecting insulin at doses of 0.1 U/kg and 0.3 U/kg. With 0.3 U/kg of insulin, the rate of fall in glycemia and the nadir of blood glucose were made similar to those with 0.1 U/kg of insulin by glucose infusion with artificial endocrine pancreas. Plasma glucagon response after 0.3 U/kg of insulin was significantly suppressed as compared to that after 0.1 U/kg of insulin, demonstrating that not only hypoglycemic stimulus but also plasma insulin concentration were important determinants responsible for glucagon secretion in insulin-induced hypoglycemia. Secondly, effect of strict glycemic control was studied. Short-acting insulin at a dose of 0.1 U/kg was injected in an intravenous bolus form into 12 insulin-dependent (IDDM) and 9 non-insulin-dependent (NIDDM) diabetics before and 1-3 months after strict glycemic control with multiple insulin injections therapy. Before strict glycemic regulations in IDDM, no significant rise in plasma glucagon concentrations was observed during the insulin-induced hypoglycemia. In NIDDM, a rise in plasma glucagon concentrations was observed, though the response was delayed. After strict glycemic regulations, in patients with residual endogenous insulin secretion, the glucagon response to hypoglycemia improved considerably in IDDM and normalized in NIDDM. In IDDM and NIDDM, improvement in glucagon response to hypoglycemia related positively to daily urinary secretion rate of C-peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

The Wearable Artificial Endocrine Pancreas with a Needle‐ Type Glucose Sensor: Perfect Glycemic Control in Ambulatory Diabetics

We have succeeded in miniaturizing a glucose monitoring system into a needle type which preserves the characteristics suitable to apply in a wearable closed‐loop control system. The wearable artificial endocrine pancreas (12 times 15 times 6 cm, 400 g) consists of the sensor, a microcomputer system which calculates insulin and glucagon infusion rates and a 2‐syringe driving system.

Validation of I.V. small-dose insulin infusion therapy in diabetic ketoacidosis of depancreatized dogs.

SummaryA validation of small-dose insulin infusion therapy was studied by the constant i.v. infusion of various doses of insulin into ketoacidotic depancreatized dogs. Constant insulin infusion of 5 × B, 10 × B, 30 × B and 50 × B (B=225 µU/kg/min) was performed for 3 h by mechanical pump. The following results were obtained: (1) plasma concentrations of immunoreactive insulin (IRI) increased proportionally to the dose of infused insulin, but the higher IRI did not result in a greater fall in plasma glucose concentration, correspondingly; the mean rate of fall in plasma glucose concentration of 5 × B was not significantly lower than that of 50 × B; β-hydroxybutyrate and arterial pH improvements were observed in each group during the 3-h insulin infusion. These data suggested that for the improvement of diabetic ketoacidosis, the insulin infusion rate of more than 30 × B, which raised the plasma IRI levels above the physiological range, was not essential; (2) the necessity of potassium supplementation during the small-dose insulin infusion was suggested if the pre-treatment level of serum potassium was low. These results confirmed that in the absence of infection or severe acidosis small-dose insulin infusion therapy is as effective as the conventional large-dose insulin therapy.

Postbulbar duodenal ulcer occurring in a patient of diabetic coma

SummaryDuodenal ulcer beyond the bulb occurred in a diabetic patient when he was in ketoacidotic coma causing serious anemia. Early investigation of the stomach and duodenum by endoscope was quite valuable for evaluating this bleeding complication and the healing process of the lesion was serially recorded. Since several cases of diabetic coma have been reported to die from gastrointestinal bleeding, this report presents the important aspect in the management of diabetic coma, and usefulness of emergency endoscope.