Coordinate regulation of amylin and insulin expression in response to hypoglycemia and fasting.
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.
Alam
T
T
Gifford Laboratories, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
Chen
L
L
Ogawa
A
A
Leffert
J D
JD
Unger
R H
RH
Luskey
K L
KL
D000682:Amyloid / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005215:Fasting / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics* / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D007003:Hypoglycemia / Q000235:genetics / Q000503:physiopathology*; D007328:Insulin / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D000078790:Insulin Secretion; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D009693:Nucleic Acid Hybridization; D010179:Pancreas / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D000682:Amyloid; D001786:Blood Glucose; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D012333:RNA, Messenger; D005947:Glucose