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Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

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Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
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Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
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Piaget's Stage 4 of Cognitive Development01:19

Piaget's Stage 4 of Cognitive Development

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The formal operational stage, as described in Piaget's cognitive development theory, begins around age 11 and extends into adulthood. It marks the emergence of advanced cognitive abilities that differentiate adolescent and adult thinking from those of younger children. This stage is characterized by abstract reasoning, hypothetical-deductive reasoning, and a more complex understanding of self and others.
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Amides to Amines: LiAlH4 Reduction01:20

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Amide reduction with strong reducing agents like lithium aluminum hydride proceeds through a nucleophilic acyl substitution to form amines. Primary, secondary, and tertiary amides yield primary, secondary, and tertiary amines, respectively.
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate.
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Nitriles are reduced to amines in the presence of strong reducing agents like lithium aluminum hydride through a typical nucleophilic acyl substitution. The reaction requires two equivalents of the reducing agent. The reducing agent acts as a source of hydride ions.
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The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
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[DPP-4 inhibitors in nephropatics].

Annamaria Bruzzese1, Maria Pasquale2, Carmela Aloisi1

  • 1UOC di Nefrologia e Dialisi, Policlinico Universitario Gaetano Martino, Messina, Italy.

Giornale Italiano Di Nefrologia : Organo Ufficiale Della Societa Italiana Di Nefrologia
|May 1, 2018
PubMed
Summary

Dipeptidyl peptidase-4 (DPP-4) inhibitors are effective and well-tolerated for managing type 2 diabetes mellitus (T2DM) in patients with advanced chronic kidney disease (CKD), including end-stage renal disease (ESRD). They demonstrated improved glycemic control without hypoglycemia or adverse effects on kidney function.

Keywords:
chronic kidney diseasediabetesdrugtollerability

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Area of Science:

  • Nephrology
  • Endocrinology
  • Pharmacology

Context:

  • Diabetic nephropathy complicates type 2 diabetes mellitus (T2DM) management, requiring careful drug selection.
  • Advanced chronic kidney disease (CKD) stages necessitate dose adjustments or avoidance of certain glucose-lowering medications.
  • Dipeptidyl peptidase-4 (DPP-4) inhibitors are approved for T2DM with CKD stages III and IV, with proposed use in end-stage renal disease (ESRD).

Purpose:

  • To evaluate the safety and efficacy of DPP-4 inhibitors in T2DM patients with advanced CKD (stage IV).
  • To compare DPP-4 inhibitors with traditional glucose-lowering drugs in a cohort of 60 T2DM patients with CKD stage IV.
  • To assess glycemic control, hypoglycemia, side effects, and impact on CKD progression.

Summary:

  • A prospective observational study compared 15 T2DM patients with CKD stage IV on DPP-4 inhibitors to those on conventional therapies.
  • DPP-4 inhibitors demonstrated superior glycemic control (hemoglobin A1c stability) compared to the control group.
  • No hypoglycemia or adverse effects on CKD progression were observed with DPP-4 inhibitors, unlike intensive insulin therapy.

Impact:

  • DPP-4 inhibitors offer an effective and safe alternative to insulin for T2DM patients with severe renal impairment.
  • Findings support the use of DPP-4 inhibitors, with potential dose adjustments, in managing T2DM patients across advanced CKD stages, including ESRD.
  • This research provides valuable insights for optimizing glucose-lowering strategies in a vulnerable patient population.