Incretin mimetics and dipeptidyl peptidase-IV inhibitors: Potential new therapies for type 2 diabetes mellitus
ABSTRACT The emergence of the glucoregulatory hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide has expanded our understanding of glucose homeostasis. In particular, the glucoregulatory actions of the incretin hormone GLP-1 include enhancement of glucosedependent insulin secretion, suppression of inappropriately elevated glucagon secretion, slowing of gastric emptying, and reduction of food intake. Two approaches have been developed to overcome rapid degradation of GLP-1. One is the use of agents that mimic the enhancement of glucose-dependent insulin secretion, and potentially other antihyperglycemic actions of incretins, and the other is the use of dipeptidyl peptidase-IV inhibitors, which reduce the inactivation of GLP-1, increasing the concentration of endogenous GLP-1. The development of incretin mimetics and dipeptidyl peptidase-IV inhibitors opens the door to a new generation of antihyperglycemic agents to treat several otherwise unaddressed pathophysiologic defects of type 2 diabetes mellitus. We review the physiology of glucose homeostasis, emphasizing the role of GLP-1, the pathophysiology of type 2 diabetes mellitus, the clinical shortcomings of current therapies, and the potential of new therapies -- including the newly approved incretin mimetic exenatide -- that elicit actions similar to those of GLP-1.
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ABSTRACT: Hematopoietic stem cell (HSC) transplantation fails if grafted HSCs fail to find and settle in an appropriate bone marrow niche where they can receive required trophic factors from stromal cells. Since intravenously injected HSCs are known to migrate into the bone marrow mainly in response to gradients of the CXCL12 chemokine, we reasoned that drugs that inhibit catabolism of CXCL12 could eventually increase the CXCL12 gradient and enhance engraftment. dipeptidyl peptidase IV (DPP-IV) catalyzes the first step in CXCL12 degradation, and oral DPP-IV inhibitors, such as sitagliptin, have been recently approved for type II diabetes mellitus. We report here a case of delayed graft failure in a T-cell-depleted (TCD) HSC transplant recipient, which was refractory to both retransplantation and high-dose granulocyte-colony stimulating factor (G-CSF). After beginning sitagliptin therapy our patient showed a sustained neutrophil rise and a reduction in transfusion dependence, which worsened again after drug discontinuation. Since these changes were paralleled by fluctuations in CXCL12 levels in serial peripheral blood samples, we discuss here the potential benefit of this class of drugs.Leukemia Research 06/2008; 33(1):178-81. DOI:10.1016/j.leukres.2008.04.019 · 2.69 Impact Factor
Article: Liraglutide[Show abstract] [Hide abstract]
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