Kazuhiko Okai

Plasma islet amyloid polypeptide (Amylin) levels and their responses to oral glucose in Type 2 (non-insulin-dependent) diabetic patients

SummaryFasting plasma islet amyloid polypeptide concentrations and their responses to an oral glucose load were determined in non-diabetic control subjects and patients with abnormal glucose tolerance in relation to the responses of insulin or C-peptide. Plasma islet amyloid polypeptide was measured by radioimmunoassay. In the non-diabetic control subjects, fasting plasma islet amyloid polypeptide was 6.4±0.5 fmol/ml (mean ± SEM) and was about 1/7 less in molar basis than in insulin. The fasting islet amyloid polypeptide level rose in obese patients and fell in patients with Type 1 (insulin-dependent) diabetes mellitus. In non-obese patients with impaired glucose tolerance and Type 2 (non-insulin-dependent) diabetic patients without insulin therapy, the level was equal to that of the control subjects, but a low concentration of islet amyloid polypeptide relative to insulin or C-peptide was observed in the non-obese Type 2 diabetic group. The patterns of plasma islet amyloid polypeptide responses after oral glucose were similar to those of insulin or C-peptide. However, compared to non-obese patients, a hyper-response of islet amyloid polypeptide relative to C-peptide was noted in obese patients who had a hyper-response of insulin relative to C-peptide. This study suggests that basal hypo-secretion of islet amyloid polypeptide relative to insulin exists in non-obese Type 2 diabetes and that circulating islet amyloid polypeptide may act physiologically with insulin to modulate the glucose metabolism.

Islet amyloid polypeptide (IAPP) secretion from islet cells and its plasma concentration in patients with non-insulin-dependent diabetes mellitus.

Islet amyloid polypeptide (IAPP/Amylin) is a novel peptide which was extracted from islet amyloid deposits in patients with non-insulin-dependent diabetes mellitus (NIDDM). However, its pattern of secretions and plasma concentrations under various conditions has not yet been made clear enough. In this study, we examined IAPP secretion from islet beta-cells in vitro using cultured islet cells of neonatal rat pancreas and plasma IAPP responses under various conditions in vivo in normal control subjects and patients with glucose intolerance. Our data revealed that (1) IAPP is co-secreted with insulin from islet cells of the rat pancreas by glucose and non-glucose stimuli; (2) fasting plasma IAPP levels in normal control subjects are 24.9 +/- 2.0 pg/ml and the molar ratio of IAPP/insulin is approximately 1/7; (3) fasting IAPP levels are high in obese patients and low in insulin-dependent diabetic patients, and the molar ratio of IAPP/C-peptide in NIDDM patients is lower than that in normal control subjects, suggesting the basal hyposecretion of IAPP relative to insulin in NIDDM; and (4) the obese patients who had a hyperresponsiveness of insulin relative to C-peptide had the hyperresponsiveness of IAPP relative to C-peptide during an oral glucose load, suggesting that IAPP may have some physiological effect in glucose metabolism.

Properdin Factor B Frequencies in Four Asian Populations

The distribution of Properdin factor B (Bf) phenotypes and their gene frequencies were investigated in four Asian populations (Chinese, Filipino, Thai and Japanese). The frequency of the BfS phenotype in Filipinos (0.717) was significantly lower than that in Chinese (0.900) and Thai (0.889) (p less than 0.01), but not different from the Japanese (0.840). One variant, BfF 0.65 S, was identified in a Japanese subject. Thus, in the Asian populations studied, Bfs frequencies were high and the frequency of variants other than F and S were low.

From Clinical Studies of Diabetes to Molecular Biology. Identification of Abnormal Insulin "Insulin Wakayama".

The recent development of molecular biology enables us to identify three abnormal insulins (insulin Chicago, insulin LosAngeles and insulin Wakayama). In Japan, three pedigrees in which affected individuals secrete [LeuA3] insulin (insulin Wakayama) have been identified. In each family, hyperinsulinemia associated with an abnormally elevated insulin to C-peptide molar ratio was demonstrated to occur in an autosomal dominant pattern of inheritance. In accordance with in vivo observations, semisynthetic [LeuA3] insulin demonstrated reduced in vitro receptor binding and biological activity relative to the human standard. The development of diabetes mellitus in affected family members was not uniform, was influenced by aging, and was different among families. Patients with impaired glucose tolerance demonstrated reduced insulin secretory reserve. Some of these features are thought to resemble the nature of noninsulin dependent diabetes mellitus (NIDDM).Therefore, insulin Wakayama may be an useful model for the study of the development of NIDDM.