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

Abstract

Fasting 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.

No correlation between insulin and islet amyloid polypeptide after stimulation with glucagon-like peptide-1 in type 2 diabetes

“…In the normal subjects, fasting circulating IAPP was approximately 4 pmol/l, which is in the range of 2-10 pmol/l found in previous studies in healthy subjects (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)21). Furthermore, in the normal subjects, there was a close correlation between circulating IAPP and circulating insulin in the fasting state, the regression coefficient being 0.74, which confirms previous studies (7,12,14).…”

“…IAPP is co-stored with insulin in the pancreatic B cells and previous studies have shown that IAPP and insulin are co-released under a variety of experimental conditions (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). However, it has also been suggested that under certain conditions IAPP and insulin are released in a non-parallel fashion.…”

“…To gain further insight into the issue of IAPP's involvement in the pathophysiology or metabolic perturbations of diabetes, it is important to establish the regulation of its circulating levels under normal conditions and in subjects with type 2 diabetes. Previous studies have shown that in normal subjects, the peptide is released simultaneously with insulin in response to oral and intravenous glucose, ingestion of a mixed meal and intravenous arginine (7)(8)(9)(10)(11)(12)(13)(14). It has also been shown that in non-diabetic obese subjects, circulating IAPP levels are elevated and the IAPP response to glucose is exaggerated compared with non-obese subjects (15,16).…”

Processing of pro‐islet amyloid polypeptide (proIAPP) by the prohormone convertase PC2

“…IAPP is colocalised with insulin in the secretory granules of islet fl-cells and co-secreted in response to fl-cell secretagogues [3,4]. IAPP has been identified in all species examined so far [5] and, in common with other secretory peptides, is synthesized as a larger precursor molecule.…”

Serum Amylin Indicates Hypertriglyceridemia in Pre-diabetics

“…Amylin has been shown to mirror insulin secretion in healthy subjects [5], obese subjects, prediabetics (subjects with impaired glucose tolerance) [6,7], and patients with Type 2 Diabetes [5]. These findings suggest an active role for plasma amylin levels in modulating glucose metabolism [8]. However, the mechanisms and the precise role of amylin in the pathophysiology of Type 2 Diabetes remains unclear.…”