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 major component is the normal beta-cell secretory product amylin, or islet amyloid polypeptide (IAPP). To determine whether increased or disproportionate release of amylin may explain the propensity for amyloid deposition in type 2 diabetes, we measured plasma amylin-like immunoreactivity (ALI) and immunoreactive insulin (IRI) release in response to an oral glucose load in 94 Japanese-American subjects with normal glucose tolerance (NGT; n=56), impaired glucose tolerance (IGT; n=10), and type 2 diabetes (n=28) as defined by World Health Organization criteria. The incremental increase in ALI, IRI, and glucose (G) at 30 min after oral glucose ingestion was used to calculate deltaALI/deltaG and deltaIRI/deltaG as measures of beta-cell function. Overall glucose metabolism was assessed as the incremental glucose area (glucose AUC) during the 2 h of the oral glucose tolerance test. As expected, plasma 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 diabetes. In response to glucose ingestion, plasma IRI and ALI increased in all subjects, but these increments were lower in individuals with reduced glucose tolerance, as reflected in the deltaIRI/deltaG (NGT, 119+/-10.3; IGT, 60.7+/-7.1; type 2 diabetes, 49.7 +/-5.4 pmol/l; P < 0.0001) and deltaALI/deltaG (NGT, 2.6+/-0.2; IGT, 1.8+/-0.3; type 2 diabetes, 1.2+/-0.1 pmol/l; P < 0.0001). Moreover, these reductions in the 30-min incremental ALI and IRI responses were proportionate such that the molar ratio of ALI to IRI was not different among the 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 deltaIRI/deltaG or deltaALI/deltaG, and glucose metabolism, assessed as glucose AUC, was nonlinear and inverse in nature, with r2 values of 0.38 (P < 0.0001) and 0.33 (P < 0.0001), respectively. 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 in type 2 diabetes is the result of increased release of ALI.
Kahn
S E
SE
Division of Metabolism, Endocrinology and Nutrition, University of Washington and VA Puget Sound Health Care System, Seattle 98108, USA.
Verchere
C B
CB
Andrikopoulos
S
S
Asberry
P J
PJ
Leonetti
D L
DL
Wahl
P W
PW
Boyko
E J
EJ
Schwartz
R S
RS
Newell-Morris
L
L
Fujimoto
W Y
WY
D000682:Amyloid / Q000097:blood*; D001213:Asian; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000208:ethnology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D058228:Islet Amyloid Polypeptide; D007564:Japan / Q000208:ethnology; D008297:Male; D008875:Middle Aged
D000682:Amyloid; D001786:Blood Glucose; D007328:Insulin; D058228:Islet Amyloid Polypeptide