REDUCED AMYLIN RELEASE IS A CHARACTERISTIC OF IMPAIRED GLUCOSE-TOLERANCE AND TYPE-2 DIABETES IN JAPANESE-AMERICANS

Islet amyloid is a characteristic feature of type 2 diabetes. Its majo r component is the normal beta-cell secretory product amylin, or islet amyloid polypeptide (IAPP). To determine whether increased or disprop ortionate release of amylin may explain the propensity for amyloid dep osition in type 2 diabetes, we measured plasma amylin-like immunoreact ivity (ALI) and immunoreactive insulin (IRI) release in response to an oral glucose load in 94 Japanese-American subjects with normal glucos e tolerance (NGT; n = 56), impaired glucose tolerance (IGT; n = 10), a nd type 2 diabetes (n = 28) as defined by World Health Organization cr iteria. The incremental increase In AI,I, IRI, and glucose (G) at 30 m in after oral glucose ingestion was used to calculate Delta ALI/Delta G and Delta IRI/Delta G as measures of beta-cell function. Overall glu cose metabolism was assessed as the incremental glucose area (glucose AUG) during the 2 h of the oral glucose tolerance test. As expected, p lasma glucose concentrations at both fasting (NGT, 5.0 +/- 0.4; IGT, 5 .5 +/- 0.1; type 2 diabetes, 6.2 +/- 0.3 mmol/l; P < 0.0001) and 2 h ( NGT, 6.7 +/- 0.1; IGT, 9.4 +/- 0.3; type 2 diabetes, 13.2 +/- 0.5 mmol /l; P < 0.0001) were elevated in individuals with IGT and type 2 diabe tes. In response to glucose ingestion, plasma IRI and ALI increased in all subjects, but these increments were lower in individuals with red uced glucose tolerance, as reflected in the Delta IRI/Delta G (NGT, 11 9 +/- 10.3; IGT, 60.7 +/- 7.1; type 2 diabetes, 49.7 +/- 5.4 pmol/l; P < 0.0001) and Delta ALI/Delta G (NGT, 2.6 +/- 0.2; IGT, 1.8 +/- 0.3; type 2 diabetes, 1.2 +/- 0.1 pmol/l; P < 0.0001). Moreover, these redu ctions in the 30-min incremental ALI and IRI responses were proportion ate such that the molar ratio of ALI to IRI was not different among th e three groups (NGT, 2.6 +/- 0.2; IGT, 2.9 +/- 0.3; type 2 diabetes, 2 .9 +/- 0.3%; NS). Further, the relationship between beta-cell function , measured as either Delta IRI/Delta G or Delta ALI/Delta G, and gluco se metabolism, assessed as glucose AUG, was nonlinear and inverse in n ature, with r(2) values of 0.38 (P < 0.0001) and 0.33 (P < 0.0001), re spectively. We conclude that the reduced beta-cell function of IGT and type 2 diabetes includes proportionate reductions in both IRI and ALI release. Thus, it is unlikely that the development of islet amyloid i n type 2 diabetes is the result of increased release of ALI.