Amylin found in amyloid deposits in human type 2 diabetes mellitus may be a hormone that regulates glycogen metabolism in skeletal muscle.

Abstract

Diabetes-associated peptide has recently been isolated and characterized from the amyloid of the islets of Langerhans in type 2 (non-insulin-dependent) diabetics, and immunoreactivity with antibodies to the peptide has been demonstrated in islet B cells of both normal and type 2 diabetic subjects. In view of the evidence presented in this paper that this 37-amino acid peptide may be a hormone present in normal individuals, we now propose the name "amylin" to replace "diabetes-associated peptide." Because increased amylin, deposited as amyloid within the islets of Langerhans, is characteristic of type 2 diabetes, the study below was performed to examine the possible effects of amylin on peripheral glucose metabolism. Whole amylin was synthesized by using solidphase techniques, with formation of the disulffide linkage by oxidation in dilute aqueous solution and recovery of the peptide by Iyophilization. The effects of amylin on glucose metabolism were studied in two preparations in vitro, isolated rat soleus muscle strips and isolated rat adipocytes. In skeletal muscle exposed to 120 nM amylin for 1 hr, there was a marked decrease in both basal and submaxmally insulin-stimulated rates of glycogen synthesis, which resulted in significant reduction in the rates of insulin-stimulated glucose uptake. In muscles treated with amylin there was no response at the concentration of insulin required to stimulate glucose uptake half-maximally in untreated (control) muscles. In marked contrast, amylin had no effect on either basal or insulinstimulated rates of glucose incorporation into either CO2 or triacylglycerol in isolated adipocytes. Therefore, amylin may be a factor in the etiology of the insulin resistance in type 2 diabetes mellitus, as both deposition of the peptide in islet amyloid and decreased rates of glucose uptake and glycogen synthesis in skeletal muscle are characteristic of this condition.

Calcitonin gene‐related peptide‐1 (CGRP‐1) is a potent regulator of glycogen metabolism in rat skeletal muscle

“…The neuropeptide calcitonin gene-related peptide (CGRP) has 46°70 primary amino acid sequence identity with the pancreatic peptide amylin [12]. Both peptides inhibit basal and insulinstimulated glycogen synthesis in incubated stripped soleus muscle preparations [10,13]. Soleus is largely populated with type I fibres.…”

“…In plasma, vWF circulates as a heterogeneous mixture of disulfide-bridged polymers ranging from dimers (Mr 25X104) to multimers (Mr>2× 107) and its role is to promote the initial step in hemostatic plug formation [4] by interacting with the subendothelial structures (collagen) of injured vessel and with the glycoprotein IIb-IIIa of activated platelets [5,6]. In the presence of the antibiotic ristocetin, vWF is capable of interacting with resting platelets too: in this case the platelet membrane glycoprotein Ib is responsible for the interaction with the ristocetin-vWF complex [7][8][9][10][11] by which platelets are activated and aggregate. Glycoprotein Ib retains the capability to interact with the ristocetinvWF complex also when platelets are metabolically [12,13]; in this case agglutination of FFP occurs.…”

Islet amyloid polypeptide/amylin messenger RNA and protein expression in human insulinomas in relation to amyloid formation

“…The major protein component of these deposits was identified as islet amyloid polypeptide (IAPP) (5,6). A peptide with the same amino acid (aa) sequence was purified from pancreatic islet amyloid in patients with type 2 (non-insulin-dependent) diabetes mellitus (7) and was named amylin (8).…”

Biotinyl analogues of amylin as biologically active probes for amylin/CGRP receptor recognition

“…Amylin, which was originally isolated from the amyloid mass in the pancreases of type 2 diabetics, has all the hallmarks of a novel glucoregulatory hormone which counteracts insulin action [2,3]. Interestingly, the neuropeptide CGRP is now known to have a high degree of functional, as well as structural, similarity with amylin.…”