Coordinate Regulation of Amylin and Insulin Expression in Response to Hypoglycemia and Fasting

Abstract

Amylin is a 37-amino acid peptide synthesized in the pancreatic beta-cell and cosecreted with insulin. In situ hybridization of nondiabetic rat pancreas shows that insulin and amylin RNA are both localized within the islet of Langerhans in a similar distribution. After 12 days of insulin-induced hypoglycemia (mean blood glucose 3.0 +/- 0.4 mM [54 +/- 8 mg/dl]), both insulin and amylin RNA fell greater than 95%. However, maintenance of euglycemia by simultaneous infusion of glucose with insulin did not suppress insulin or amylin RNA. Fasting suppressed amylin and insulin secretion from the isolated, perfused pancreas 70 and 58%, respectively, and with refeeding, secretion rates recovered to fed levels. Despite these changes in the rates of secretion, the relative ratio of amylin to insulin was not significantly different in fed, fasted, or refed rats. The molar ratio of insulin to amylin was estimated to be 100:2.3-2.6. Both insulin and amylin RNA was suppressed approximately 50% in response to fasting. Thus, although the absolute amounts of insulin and amylin change substantially under the conditions tested, the relative amounts of these peptides do not change.

Glucose Regulates Islet Amyloid Polypeptide Gene Transcription in a PDX1- and Calcium-dependent Manner

“…Transcription of the IAPP (8,9) and insulin (10) genes is also stimulated by glucose. In the case of insulin, multiple cis-acting elements located within a relatively short region (Ϫ1 to Ϫ360) upstream of the start site contribute to the regulation of the gene by glucose and other nutrients (11).…”

Islet amyloid polypeptide in the islets of Langerhans: friend or foe?

“…In adult animals, IAPP expression occurs in pancreatic and gastrointestinal somatostatin (D)-cells [64] as well as in primary sensory neurons [12], cell types which all clearly lack insulin expression. It should be noted that in response to changes in ambient glucose concentrations in vivo, islet IAPP and insulin mRNA expressions appear to be regulated in parallel [70,71].…”

Beating diabetes: strategies to improve pancreatic islet transplantation

“…This three-dimensional shape has been shown to be critical for optimal beta-cell functioning [40]. The homogenous human islet cell aggregates can easily be harvested from the microwells in high quantities, after which they remain stable and can be used for further investigation or transplantation.…”

“…Amylin is co-secreted with insulin by beta-cells (molar ratio amylin to insulin is approximately 2:100) [40], somatostatin is produced by delta-cells (<10% of total islet cells), and pancreatic polypeptide is produced by PP-cells (<5% of cells) [36]. Pancreatic polypeptide does not contain any tryptophan or cysteine groups, reflected by the absence of the corresponding Raman bands.…”

“…Connexins 36 and 43 are known to play an important in the regulation of pancreatic islet function [38]. Connexin 36 is associated with the regulation of beta-cell gap junctions, while connexin 43 is believed to mediate other islet-cell type channels [39,40]. In addition, cell adhesion molecules (CAMs) such as integrins, neural cell adhesion molecule (N-CAM), and epithelial-cadherin (E-CAD) play an important role in cell-cell interactions [18,41,42].…”