title: Altered activities of kininase II, an angiotensin converting enzyme, prekallikrein, and nitric oxide in Kuwaiti patients with type 2 diabetes.
abstract: The current investigation was conducted to examine kininase II or angiotensin converting enzyme (ACE), plasma prekallikrein (PK), and nitric oxide (NO) concentrations in healthy Kuwaiti subjects and newly diagnosed Kuwaiti type 2 diabetic patients before and after treatment for 6 weeks with metformin hydrochloride 500 mg twice daily after meal. With the consent of volunteers, blood and urine samples were collected after an overnight fasting. Samples were collected from the diabetic patients before and after treatment for 6 weeks. Enzyme linked immunosorbent assay (ELISA) was carried out on the aliquoted samples to measure the concentration of kininase II. NO was detected via colorimetry. Plasma Kininase II or ACE levels were significantly (P <0.01) increased by 18% in untreated diabetics when compared with healthy volunteers. However, after treatment there was a significant decrease of 20% in their ACE levels. Plasma prekallikrein levels were raised significantly (P <0.01) by 28% in diabetic patients in contrast with the control subjects and the levels were significantly reduced (P <0.0001) by 44% after treatment with metformin hydrochloride. NO levels were found to be significantly decreased in plasma by 56% and in urine by 62% in untreated diabetic patients as compared with the healthy subjects. However, when the treated diabetic patients were compared with untreated diabetics, there was an increase of 50% in plasma and 37% in urine samples. The high levels of kininase II, prekallikrein, and reduced NO may be partly responsible for the induction of renal, cardiac, and hypertensive complications associated with type 2 diabetes. Reduced NO level is an indication of endothelial dysfunction resulting in increased blood pressure. Oral anti-diabetic treatment is associated with protective effects through the reduction of kininase II (ACE), prekallikrein, and elevation of NO levels.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Health Sciences Centre, Kuwait University, Safat, Kuwait j.n.sharma@hsc.edu.kw.
authors.forename: J N
authors.initials: JN
authors.lastname: Sharma
authors.affiliation: Department of Medicine, Division of Endocrinology, Faculty of Medicine, Health Sciences Centre, Kuwait University, Safat, Kuwait.
authors.forename: Kas
authors.initials: K
authors.lastname: Al-Shoumer
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Health Sciences Centre, Kuwait University, Safat, Kuwait.
authors.forename: K M
authors.initials: KM
authors.lastname: Matar
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Health Sciences Centre, Kuwait University, Safat, Kuwait.
authors.forename: N V
authors.initials: NV
authors.lastname: Madathil
authors.affiliation: Al-Shohada Specialist Health Center, Ministry of Health, Kuwait.
authors.forename: Amk
authors.initials: A
authors.lastname: Al-Moalem
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism; D007730:Kuwait; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011288:Prekallikrein / Q000378:metabolism*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D009569:Nitric Oxide; D011288:Prekallikrein; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: diabetes mellitus; kininase II; metformin; nitric oxide; prekallikrein