ArticlePloS one2014
Preclinical characterization of recombinant human tissue kallikrein-1 as a novel treatment for type 2 diabetes mellitus.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 20 citations in OpenAlex.
- Genome-Wide Discovery Reveals Adipose-Specific and Systemic Regulators of Insulin Resistance.medRxiv : the preprint server for health sciences · 2026Article
- A Phase 1C, Open Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of DM199 Administered Intravenously with a Polyvinyl Chloride Bag in Adult Healthy Subjects and Adults Recently Taking Angiotensin-Converting Enzyme Inhibitors.Clinical pharmacology in drug development · 2025Article
- Serendipitous Discovery of T Cell-Produced KLK1b22 as a Regulator of Systemic Metabolism.ImmunoHorizons · 2023Article
- Kinins and Kinin Receptors in Cardiovascular and Renal Diseases.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Trends in Antidiabetic Drug Discovery: FDA Approved Drugs, New Drugs in Clinical Trials and Global Sales.Frontiers in pharmacology · 2021Review
- Early metabolic markers identify potential targets for the prevention of type 2 diabetes.Diabetologia · 2017Article
- Plasma metabolomic profiles in association with type 2 diabetes risk and prevalence in Chinese adults.Metabolomics : Official journal of the Metabolomic Society · 2016Article
- Pharmacological effects of recombinant human tissue kallikrein on bradykinin B2 receptors.Pharmacology research & perspectives · 2015Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Modulation of the kallikrein-kinin system (KKS) has been shown to have beneficial effects on glucose homeostasis and several other physiological responses relevant to the progression of type 2 diabetes mellitus (T2D). The importance of bradykinin and its receptors in mediating these responses is well documented, but the role of tissue kallikrein-1, the protease that generates bradykinin in situ, is much less understood. We developed and tested DM199, recombinant human tissue kallikrein-1 protein (rhKLK-1), as a potential novel therapeutic for T2D. Hyperinsulinemic-euglycemic clamp studies suggest that DM199 increases whole body glucose disposal in non-diabetic rats. Single-dose administration of DM199 in obese db/db mice and ZDF rats, showed an acute, dose-dependent improvement in whole-body glucose utilization. Sub-acute dosing for a week in ZDF rats improved glucose utilization, with a concomitant rise in fasting insulin levels and HOMA1-%B scores. After cessation of sub-acute dosing, fasting blood glucose levels were significantly lower in ZDF rats during a drug wash-out period. Our studies show for the first time that DM199 administration results in acute anti-hyperglycemic effects in several preclinical models, and demonstrate the potential for further development of DM199 as a novel therapeutic for T2D.
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