To determine whether erythrocytes behave like other insulin target cells such as adipocytes in regard to their insulin binding, we studied the insulin binding of erythrocytes and adipocytes rom the same rat.
In order to test affinity changes of the insulin recepors, we used 48-hour fasted rats, and for changes in insulin receptor number, we compared the insulin binding of lean young rats and old obese rats.
With 48 hours fasting, the affinity of the insulin receptors increased in both erythrocytes and adipocytes from lean rats. However, in obese rats, there were no significant changes in the affinity of the receptors in both erythrocytes and adipocytes from fasted rats.
As for changes in the receptor number, a 50% decrease in insulin receptor number was noted in both erythrocytes and adipocytes from obese rats.
A close relationship existed between the insulin binding at an insulin concentration of 0.2 ng/ml and the plasma insulin levels both in erythrocytes (r=-0.556, p<0.05) and adipocytes (r=-0.503, p<0.05). Furthermore, there was a close relationship in insulin binding between erythrocytes and adipocytes (r=0.685, p<0.01).
It is apparent from the above results that rat erythrocyte insulin receptors mirror changes in the insulin receptors of other insulin target cells such as adipocytes.

View full abstract

The properties of the insulin receptors on plasma membranes isolated from human hepatoma were studied in comparison with those from normal liver. The plasma membranes from human hepatoma and normal liver bound specifically to insulin and had at least two classes of insulin receptor sites in respect of their affinity and capacity. 1251-insulin binding in the hepatoma was higher than that of the normal liver at either 4°, 22° or 37°C.
When analyzed from Scatchard plots, the affinity constant of the hepatoma was lower than that of the normal liver. The binding capacity of the hepatoma, however, was higher than that of the normal liver. The average total binding capacity (high affinity plus low affinity) was significantly higher than that in the normal liver (p<0.05)
As for the proteolytic activity of the membrane preparation, only 7% of both 125I-insulin and receptors was degraded on incubation at 4°C for 24hr, whereas 23% of insulin was degraded at 37°C for 5hr. Of the proteolytic inhibitors examined, phenylmethylsulfonyl fluoride strongly prevented the degradation of insulin in the hepatoma.
These results suggest that tumorigenesis may induce changes in the properties of insulin receptors on plasma membranes.

View full abstract

An association between elevated serum insulin levels and hypertension or cardiovascular diseases has long been noted, implying possible effects of hyperinsulinemia on the development of atheroseclerosis. A recent epidemiological study carried out in Helsinki also foundthat hyperinsulinemia could be a risk factor for coronary heart disease. The present authors studied the serum insulin response during 50g OGTT in subjects with hypertension, arteriosclerosis and abnormal lipid metabolism, in order to elucidate these relationships.
(1) The subjects were 219 people aged 40 years or more, who were admitted for health check-ups at our institute, with no family history of diabetes, with normal glucose tolerance (ΣBG<350) and with normal liver function tests (GOT, GPT, ZTT).
(2) The insulin levels were found to be higher before and after glucose loading in the subjects with hypertension than in those without hypertension, for both the non-obese and obese groups. Since, among 6 kinds of indices for evaluating insulin response established by the authors, ΣIRI indicated a sharp increase in the hypertensive subjects, an increase in total amount of insulin secretion during OGTT was suggested.
(3) The subjects with coronary heart disease and those with decreased renal function tests revealed increased ΣIRI levels independently of the effect of hypertension. The subjects with arteriosclerotic changes in the ocular fundus and those with elevated serum cholesterol or triglyceride levels showed higher insulin levels only in the normotensive group.

View full abstract

C.R. Kahn and his co-workers have reported cases of insulin-receptor autoantibodies among patients with insulin resistance. The detection of insulin-receptor autoantibodies in this paper was made by using the human placental membrane method described previously.
The subjects comprised 61 cases who were divided into three groups:(1) those whose diabetes control needed more than 80 units of insulin per day;(2) those whose fasting IRI was more than 50 pu/ml even with glucose intolerance; and (3) those who had hypoglycemia of unknown origin.
Eleven serum samples from eleven healthy women and six from six diabetics treated with insulin, and thus having insulin antibodies in their serum, were used as controls.
The binding of ¹²⁵I-insulin with human placental membranes was not suppressed by either the direct or preincubation methods on adding the serum of healthy subjects. The direct method represents a way of simultaneously incubating ¹²⁵I-insulin, membrane and patient serum. The preincubation mathod represents a way to incubate ¹²⁵I-insulin and pre-washed membrane after one day of preincubation of the membrane with patient serum. The binding of ¹²⁵I-insulin by the direct method was markedly suppressed by the serum of the insulin-treated diabetics, while such suppression was not observed by the preincubation method.
In six patients-two males and four females-among the 61, inhibition of the binding of ¹²⁵Iinsulin with the membranes was shown by both the direct and preincubation methods. Evidence of the inhibition was found in the protein fraction of the serum from these six patients, particularly in the IgG fraction of four. Three of the six patients had Sjögren syndrome, with one of these also having acanthosis nigricans. Four of the six patients showed insulin resistance, while one of the remaining two had spontaneous hypoglycemia.
A follow-up check revealed that, in three of the six cases, the antibodies decreased relatively quickly, paralleling the degree of inhibition of the binding action and occurrence of hypoglycemic attacks.
The present paper thus demonstrates the existence of patients with insulin receptor antibodies but without insulin resistance, as evidenced by the six patients identified through the human placental membrane method.

View full abstract

In order to examine the possible role of the exocrine pancreas in endocrine pancreatic functions, the levels of insulin and glucagon secretion in the isolated and perfused pancreas of rats were measured. The rats were divided into two groups. The first had atrophic exocrine pancreatic tissues subsequent to ligation of the pancreatic duct, and the second received a sham-operation.
The levels of insulin release in response to 16.7 mM glucose and 6.4 mM arginine showed similar patterns in both groups. On the other hand, the glucagon response to arginine was significantly increased in the group with exocrine pancreatic insufficiency compared to the sham group.
Histological examinations revealed a marked increase in the number of A cells in the pancreatic islets of rats with experimentally induced exocrine pancreatic insufficiency.
It was thought that in the exocrine pancreatic insufficiency, the pancreatic glucagon response to arginine was probably enhanced due to the proliferation of A cells. These results suggested that the existence and function of the exocrine pancreas exerts some influence on the functions of the A cells of islets.

View full abstract

A 47-year-old diabetic woman with moderate renal disturbance and mitral insufficiency had unexplained hyperkalemia, which was aggrevated by sodium restriction and pragressed after severe hyperglycemia improved and edema disappeared. The plasma renin activity (PRA) and plasma aldosterone concentration (PA) were low and unchanged by two-hours standing or infusion of furosemide. The plasma cortisol level and response to ACTH stimulation were normal. The responses of PA to ACTH and angiotensin II infusion were slightly decreased, but the plasma deoxycorticosterone and corticosterone after such stimulations were normal. Following infusion of 50 g glucose, there was a paradoxical increase in serum potassium levels in this patient. Histologically, the juxtaglomerular apparatus was not completely observed, but partial hyalinization of afferent arterioles was not observed. The abnormalities of potassium homeostasis in this patient were probably related to insulin and aldosterone combined deficiency.

View full abstract

The major difficulty in surgery for insulinomas occurs when no lesion can be palpated at exploration. Blind partial pancreatectomy is unsatisfactory since it removes only 25 to 55% of insulinomas. About 10% of the benign tumors are multiple and the tumors may be found outside the pancreas. Also they are apt to be overlooked at exploration. In 15-30% of patients with insulinoma, additional surgery is required.
Preoperative localization of insulinomas by arteriography is successful in only about 66% of cases. Additional preoperative studies on localization procedures are thus required.
Percutaneous transhepatic catheterization of the portal system and blood sampling for insulin radioimmunoassay were performed in a 16-year-old male with clinical evidence suggesting the presence of an insulinoma after negative selective arteriography. “Step-up” gradients in insulin levels occurred at two sites and provided good evidence for the presence of two secreting tumors in the head and tail of the pancreas.
A tumor blush was demonstrated at the head of the pancreas by repeated super-selective dorsal pancreatic arteriography, but not tumor was indicated in the tail of the pancreas.
At surgery, a small adenoma (1.5×1.0 cm) was found in the head of the pancreas as predicted by both arteriography and the catheterization procedure, and on careful palpation a very small adenoma (0.5×0.6 cm) was also found in the tail of the pancreas as predicted by the catheterization procedure.
Our experience with this patient suggests that the present catheterization procedure may be very useful for the preoperative identification of insulin-producing tumors of the pancreas.

View full abstract

Clinical application of two kinds of glucagon RIA Kits, “Daiichi” and “Dainabot”, was evaluated. Values for glucagon immunoreactivity (GI) assayed by both Kits were satisfactory as regards precision, as confirmed by withinassay, betweenassay, recovery and the dilution effect. The minimum detectable GI concentration was 31.3 pg/ml with “Daiichi”, and 50 pgind with “Dainabot”. The GI levels in fasting plasma of normals (n =16) and of patients with liver cirrhosis (n= 15), chronic renal failure (n=15) and diabetes mellitus (n=45) were assayed by both Kits and another RIA system employing antiglucagon antiserum 30 K. A significant correlation was noted between any two of the three GI assay systems.
Using the three assay systems, similar patterns of GI-response after an intravenous injection of 4 g arginine were observed; i.e., rapid increments of GI levels after the injection in both normals (n=6) and diabetics (n=6), and a larger degree of GI increment in the diabetics than the normals.
Based on the above results, the glucagon RIA Kits are recommended for plasma GI measurements.

View full abstract