Takehiko Ide

Positive Correlation of Serum Lecithin: Cholesterol Acyltransferase Activity with Relative Body Weight

Abstract. The activity of serum lecithin:cholesterol acyltransferase (LCAT) was measured in 33 subjects who had no apparent diseases except obesity in some cases. Their liver function tests were all within normal limits. The correlations of serum LCAT activity with sex, age, glucose tolerance, relative body weight, basal immunoreactive insulin, and fasting serum cholesterol and triglyceride were studied. – The results indicate that an increase in serum LCAT activity is significantly correlated with increases in relative body weight, serum total cholesterol, serum unesterified cholesterol, serum basal immunoreactive insulin, and serum triglyceride. – At present the physiological significance of serum cholesterol es‐terification is not fully established. However, the present findings suggest an increased turnover of serum esterified cholesterol in obese subjects.

Immunological reactivity of insulin to sepharose coupled with insulin-antibody---its use for the extraction of insulin from serum.

Abstract Anti-insulin serum globulin fraction coupled to agarose (Sepharose 2B) bound labeled and nonlabeled insulin at pH 8.2–8.4 by a specific antigen-antibody reaction. Insulin bound to this matrix was dissociated with 1 M acetic acid. Anti-insulin globulin-coupled agarose could be used repeatedly after regeneration of its insulin-binding capacity by washing with Tris-HCl-albumin buffer (pH 8.2–8.4). The column of this matrix appeared of practical value to extract insulin from serum.

The effect of fasting plasma glucose variability on the risk of retinopathy in type 2 diabetic patients: Retrospective long-term follow-up

AIMS This study aimed to determine whether fasting plasma glucose (FPG) variability can predict diabetic retinopathy development and progression independently of glycemic control. METHODS Subjects consisted of 170 type 2 diabetes mellitus patients not showing diabetic retinopathy on their first visit to our hospital between 1966 and 1979, and continuously visited thereafter for 27-40 (mean, 33) years. Plasma glucose and HbA1c data obtained on every hospital visit were collected. As FPG variability parameter, standard deviations (SD) were used. RESULTS The investigation in which patients were classified based on the median value of the mean HbA1c or FPG and that of FPG SD have revealed that the risk of retinopathy development and progression were similar between the group showing good control and high variability and that with poor control and low variability. In multivariate analysis models with the mean FPG or HbA1c as a covariate and models using the mean FPG or HbA1c as a time-dependent covariate after adjustment for age, sex, diabetes duration, BMI, hypertension, and hypoglycemia, FPG SD was a significant independent risk factor for retinopathy. CONCLUSION In type 2 diabetic patients, FPG variability is a risk factor for diabetic retinopathy independent of the mean FPG or HbA1c.

Effect of Intrapancreatic Injection of Potassium and Calcium on Insulin and Glucagon Secretion in Dogs

Acute changes in plasma immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) levels in the pancreatic vein of dogs were studied following rapid pulse injections of CaCl2, KCl and glucose into the pancreatic artery. Blood from the pancreatic vein was taken continuously by changing the collection tubes every five seconds. IRI secretion was stimulated by all three agents within thirty seconds, while IRG secretion was stimulated by the injection of KCl but not by CaCl2 or glucose. Detailed comparisons of IRI responses revealed that IRI release occurred most rapidly after the injection of KCl and most slowly after the injection of glucose. Stimulation of IRI and IRG release occurred simultaneously after KCl injection. The data suggest that potassium stimulates α and β cells directly, without increasing calcium influx. The slower insulin-releasing effect of glucose, as compared with the cations, supports the theory that glucose acts by increasing calcium uptake.

The effects of fasting plasma glucose variability and time-dependent glycemic control on the long-term risk of retinopathy in type 2 diabetic patients

Long-term fasting plasma glucose (FPG) variability was a risk factor for proliferative diabetic retinopathy (PDR) independent of the mean FPG or HbA1c in people with type 2 diabetes. PDR development was also significantly associated with mean HbA1c more than 5 years earlier and with mean FPG more than 10 years earlier.

FREQUENCY, DEGREE, AND PROGRESSION WITH TIME OF PROTEINURIA IN DIABETIC PATIENTS

Abstract The frequency of proteinuria in 333 Summary patients attending a diabetes clinic regularly for at least four years was analysed. Frequency of + + or more proteinuria at the initial visit increased from 4·0% in a subgroup with known duration of diabetes of less than one year, to 16·4% when known duration exceeded ten years. Among the groups which, on the basis of repeated fasting blood-sugar measurement, were judged as achieving good control during follow-up, the frequency of progression of proteinuria was low and was unrelated to the pretreatment fasting blood-sugar.

Effects of Hypoglycemic Sulfonamides on Glucagon and Insulin Secretion in Ducks and Dogs

Infusions of tolbutamide (1 mg./kg. min.), glibenclamide (2.5 μg./kg. min.), or glymidine Na (1 mg./kg. min.) in ducks produced a prompt fall in plasma immunoreactive glucagon (IRG), a prompt rise in plasma immunoreactive insulin (IRI) and a subsequent fall in plasma glucose. In dogs, the infusions of these three sulfonamide drugs also caused a rise in IRI and subsequent hypoglycemia, but no specific changes in IRG level in the pancreatic vein and the femoral artery. The infusion of glibenclamide (0.013 μg./kg. min.) into the pancreatic artery of a dog increased IRI secretion and produced a fall in plasma glucose but did not affect IRG level in the pancreatic vein. Carboxytolbutamide, which lacks hypoglycemic activity, failed to influence IRG and IRI in ducks. The results suggest that the hypoglycemic effect of sulfonamide drugs is mediated by insulin release and, in ducks but not in dogs, by suppression of glucagon secretion. The cause of this species difference is unknown, but the present results and additional data suggest that ducks may be much more dependent than dogs on glucagon for carbohydrate metabolism.

Comparison of the Early Time Courses of the Release of Insulin That Follow Injections of Tetragastrin, Tolbutamide, Xylitol, and Glucose into the Pancreatic Artery of Dogs

The early time courses of insulin release were studied by injecting insulinotropic substances directly into a dogs pancreatic artery. Blood samples from the pancreatic vein were collected every five seconds continuously over 90 seconds and were assayed for their insulin concentrations. Injections were repeated two to five times, with intervals of 30 minutes. Insulin release was stimulated within one minute after injection of each of tetragastrin, tolbutamide, xylitol, and glucose, but the time courses of the release of insulin were different with different stimulants: Tetragastrin and tolbutamide increased insulin release faster than did glucose; xylitol produced a slower insulin release than did glucose. The slower insulin-releasing effects of glucose and xylitol than the other agents would be compatible with the theory that their metabolism is required to cause release of insulin, but it is also possible that the glucoreceptor mechanism may require a longer lag time than the other receptor mechanisms for the perception and transfer of the signal to release insulin.

Insulin-like Activity by Fat Pad Assay and Immunoreactive Insulin: II. Their Occurrence in Fractions by Gel Filtration of Serum

In a previous report, serum insulin was extracted with efficient recovery by salt-ethanol extraction. As the second method of separation of serum insulin gel filtration was adopted. Dog sera obtained from the pancreatic and the femoral veins were separated into two fractions (A and B) with Sephadex G-50. Fractions A and B corresponded respectively to the major peak of serum proteins and the portion where I-131-insulin added to serum was eluted. Insulin-like activity (ILA) was assayed by rat fat pad and immunoreactive insulin (IRI) by a double antibody method. Significant ILA was demonstrated in both fractions. IRI in serum appeared mostly in fraction B. ILA/IRI ratio was closer to 1.0 in fraction B than in serum. Fraction A tended to have fairly uniform ILA irrespectively of origin of serum, often exceeding the ILA of serum. Fraction A from a depancreatized dog serum had similar degree of ILA. Serum and both fractions stimulated various phases of fat pad metabolism similarly to insulin, including glycogen synthesis. Assays based on four different metabolic parameters gave essentially the same ILA values for both serum and fractions. ILA of fraction A differed from insulin in its nonneutralizability with anti-insulin serum, its poor suppressibility by cysteine, and the lack of parallelism of its regression line with that of insulin. Simple dilution and reconcentration of serum resulted in an increase in its ILA. Presumably, fraction B is primarily due to serum insulin with similar immunological and biological activities to pancreatic insulin. Whether or not ILA of fraction A is related to insulin remains unknown.

Plasma insulin response to intravenous administration of tetragastrin (C-terminal tetrapeptide amide of gastrin) in man

Abstract Intravenous injection of 150 μg tetragastrin (Carbobenzoxy-L-tryptophanyl-L-methionyl-L-aspartyl-L-phenylalanine amide) resulted in a prompt and short-lived rise in plasma insulin concentration in healthy male volunteers. The concurrent infusion of glucose appeared to augment the plasma insulin response to the i.v. injection of tetragastrin. Intravenous injection of tetragastrin with glucose infusion produced a nearly normal rise in plasma insulin also in achlorhydric subjects. No significant difference was observed between the response of insulin to i.v. tetragastrin with glucose infusion in normal volunteers and achlorhydric subjects. Following the tetragastrin injection, plasma glucose increased slightly and free fatty acid tended to decrease. The slow infusion of 150 μg tetragastrin also tended to elicit a transient rapid rise in plasma insulin and a fall in free fatty acid without blood sugar change. The slow infusion of tetragastrin with glucose failed to augment the insulin response to the glucose infusion alone. Subcutaneous injection of 150 μg tetragastrin caused no changes in plasma insulin, glucose or free fatty acid.