Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The responsiveness of renin-angiotensin and kallikrein-kinin systems to furosemide challenge has been investigated in forty-six diabetic patients (34 NIDDM/12 IDDM), subdivided into Group I (uncomplicated DM), Group II (DM with hypertension), Group III (DM with nephropathy), Group IV (DM with hypertension and nephropathy) and a control group of 10 healthy volunteers. Plasma renin activity (PRA) was estimated by radioimmunoassay in blood samples drawn before and 10 min after furosemide administration (0.5 mg/kg i.v.). Urinary kallikrein levels were measured by bioassay using estrogenized rat uterus preparation in 4h urine samples collected before and after the diuretic. Urinary Na+ and K+ were also measured. The basal PRA in diabetics was not significantly different from controls, whereas, urinary kallikrein levels were markedly low in all patients. Both PRA and kallikrein levels increased after furosemide in controls while in diabetics this response was severely blunted. In a subset of Group I, a paradoxical fall in PRA and kallikrein levels was noted after furosemide, an effect similar to that observed in patients with nephropathy (Group III). This response in absence of clinical and biochemical parameters of nephropathy indicates early derangement of renal hemodynamic mechanisms heralding the onset of nephropathy.
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PMID:Plasma renin activity and urinary kallikrein excretion in response to intravenous furosemide in diabetic patients. 208 34

1. Diabetes mellitus type I was induced in 3-month old male C57 BL/KS-mdb mice (N = 24) by ip injection of streptozotocin (STZ, 45 mg/kg body weight) for 5 days. 2. To determine the possible protective effects of nitric oxide inhibition against hyperglycemia, the STZ-diabetic rats received two doses of NG-nitro-L-arginine- methyl ester (L-NAME) (10 mg/kg body weight and 10 mg/mouse) dissolved in PBS for 45 consecutive days. Another group of STZ-treated rats was similarly treated with L-arginine (5 mg/mouse). 3. Blood glucose levels were 118 +/- 37 mg/dl after 8 days of L-NAME administration (10 mg/kg body weight, N = 12) and 186 +/- 22 mg/dl (N = 12) after 5 days of L-NAME administration at the 5 mg/mouse dose. Treatment with L-arginine (5 mg/mouse, N = 12) caused a significant increase in blood glucose level to 151 +/- 17.5 mg/dl, showing the relevance of nitric oxide formation in this type of diabetes. 4. In STZ-diabetic mice treated with L-NAME (N = 12), diuresis was reduced by approximately 58% compared to STZ animals, whereas in L-arginine-treated animals (N = 12) diuresis returned to STZ levels. Urinary protein excretion, which was significantly affected by STZ (123% compared to control) was significantly reduced by 66% after treatment with L-NAME for 45 days, whereas treatment with L-arginine caused a return to STZ values. 5. Urinary kallikrein excretion, which was reduced by 80% in STZ mice compared to control, returned to control levels after L-NAME treatment. 6. The present results suggest a relationship between nitric oxide levels and the reduction of diabetic state and improved renal function by L-NAME.
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PMID:Streptozotocin-induced hyperglycemia is decreased by nitric oxide inhibition. 774 93

The aim of this study was to determine the influence of metabolic control of diabetes on natriuresis, the effect of natriuretic peptides and renal kallikrein on the kidney and the participation of proximal and distal tubules in natriuresis. The study was done in 41 individuals: 27 IDDM patients and 14 healthy controls. The patients were on insulin only, had normal blood pressure, and were prescribed a standard diabetic diet without sodium or protein restriction. Diabetic patients were assigned to subgroups, depending on the stage of nephropathy and level of metabolic control. Urine collection was done three times daily in all participants. The first collection was done after 500 mg lithium carbonate (p.o.) and was followed by 10 mg amilorid (Midamor, Thomas Morson Pharmaceuticals). The third collection of urine was used to evaluate excretion of cGMP. In addition to sodium, lithium, potassium and creatinine clearances, excretion of renal kallikrein, and levels of microalbuminuria, fructosamine and glycated hemoglobin were also determined. Lithium clearance was used to evaluate tubular sodium transport. The influence of diuretic peptides--ANP and urodilatin, on natriuresis was reflected by urinary cGMP excretion. Function of the kallikrein-kinin system was studied on the basis of excretion of kallikrein. Amilorid was used to test the effect of blocking amiloride-sensitive sodium channels in distal tubules on natriuresis (Tab. 1). A statistically significant decrease in mean lithium clearance was observed in IDDM patients as compared to healthy controls. Creatinine clearance was the same in both groups (Tab. 2). Lower lithium clearance was observed in the subgroup of diabetic patients with "silent" nephropathy. Diabetic patients with "silent" and early nephropathy had significantly higher levels of fractional sodium reabsorption in the proximal tubule when compared with controls (Tab. 3). Moreover, lower daily excretion of kallikrein was observed in patients with stage II nephropathy in comparison to the control group (Tab. 4). Amilorid uptake had no influence on urinary kallikrein. However, natriuresis after amilorid was significantly higher in diabetic patients than in controls. In conclusion, reabsorption in the proximal tubule is increased in patients with "silent" diabetic nephropathy, as revealed by decreased lithium clearance and unchanged creatinine clearance. Hyperactivity of the proximal tubule in stage II and III of diabetic nephropathy results in increased sodium reabsorption in the proximal tubule, as reflected by the increase in fractional sodium reabsorption in this tubule. Amilorid, a distal tubule blocker, reduces distal tubule activity independently of urinary kallikrein excretion. Elevated natriuresis was observed after amilorid without any change in urinary kallikrein excretion.
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PMID:[Regulation of natriuresis in diabetic nephropathy]. 1171 8

The kallikrein-kinin system (KKS) comprises a cascade of proteolytic enzymes and biogenic peptides that regulate several physiological processes. Over-expression of tissue kallikrein-1 and modulation of the KKS shows beneficial effects on insulin sensitivity and other parameters relevant to type 2 diabetes mellitus. However, much less is known about the role of kallikreins, in particular tissue kallikrein-1, in type 1 diabetes mellitus (T1D). We report that chronic administration of recombinant human tissue kallikrein-1 protein (DM199) to non-obese diabetic mice delayed the onset of T1D, attenuated the degree of insulitis, and improved pancreatic beta cell mass in a dose- and treatment frequency-dependent manner. Suppression of the autoimmune reaction against pancreatic beta cells was evidenced by a reduction in the relative numbers of infiltrating cytotoxic lymphocytes and an increase in the relative numbers of regulatory T cells in the pancreas and pancreatic lymph nodes. These effects may be due in part to a DM199 treatment-dependent increase in active TGF-beta1. Treatment with DM199 also resulted in elevated C-peptide levels, elevated glucagon like peptide-1 levels and a reduction in dipeptidyl peptidase-4 activity. Overall, the data suggest that DM199 may have a beneficial effect on T1D by attenuating the autoimmune reaction and improving beta cell health.
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PMID:Autoimmune diabetes is suppressed by treatment with recombinant human tissue Kallikrein-1. 2525 10

The central function of the immune system is to protect the host from environmental agents such as microbes or chemicals, thereby preserving the integrity of the body, and preventing the onset of illness and infection. Moreover, the immune system is constantly challenged to discriminate self vs. non-self and mediate the correct response, a phenomenon called self-tolerance. The failure of mechanisms responsible for self-tolerance and induction of an immune response against components of the self, induces autoimmunity and culminates however, in several autoimmune diseases. The precise etiology of autoimmune diseases is not known, although the classic sign of an autoimmune disease is inflammation. In this context, kinins are a family of peptides involved in different physiological and pathological states, comprising inflammatory, vascular and pain processes, and are highly relevant as well as to a variety of diseases including hypertension, kidney diseases, Alzheimer's disease, cancer, obesity, epilepsy and traumatic injuries. These kinin effects are mediated by two related G-protein-coupled receptors named the bradykinin receptors (BKRs), B1 and B2. The kallikrein-kinin system (KKS) and their receptors appear to be involved in both the development and progression of autoimmune diseases, suggesting that modulators of BKRs, administered in monotherapy or in combination with existing therapies, may represent a potential new venue for an effective autoimmune disease treatment. This review article highlights historical and recent progress in understanding the role of BKRs as potential therapeutics for a number of autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, type I diabetes mellitus, inflammatory bowel diseases, and others.
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PMID:Kinin receptors: Key regulators of autoimmunity. 2798 30