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Biomedical subjects

R G Larkins

Publications and source records attributed to R G Larkins.

At least 37 records · Page 2Linked to original sources
PubMed1995

Increased hyaluronan production in the glomeruli from diabetic rats: a link between glucose-induced prostaglandin production and reduced sulphated proteoglycan.

Exposure in vivo or in vitro to elevated glucose increases production of vasoactive prostaglandins by glomeruli and mesangial cells. This study aimed to determine whether this increased prostaglandin production could provide a link with later structural changes in diabetic nephropathy. Glomerular cores were prepared from control rats and streptozotocin-diabetic rats (3 weeks' duration). Over 24 h in culture hyaluronan production from diabetic glomerular cores was higher than production from control glomerular cores whether maintained in 5.6 mmol/l glucose (105.6 +/- 15.5 vs 53.6 +/- 8.5 ng hyaluronan per 250 glomerular cores, p < 0.001); in 25 mmol/l glucose (149.3 +/- 34.8 vs 62.7 +/- 7.8 ng hyaluronan per 250 glomerular cores, p < 0.01); or in 45 mmol/l glucose (176.8 +/- 23.3 vs 102.0 +/- 17.9 ng hyaluronan per 250 glomerular cores, p < 0.01). At 5.6 mmol/l glucose, exposure in vitro to prostaglandin E2 caused an increase in hyaluronan production [maximal at 10(-9) mol/l prostaglandin E2, 237 +/- 19 vs 42 +/- 4, ng hyaluronan per 250 glomerular cores, p < 0.001 (control) and 195 +/- 7 vs 103 +/- 5, ng hyaluronan per 250 glomerular cores, p < 0.001 (diabetic)]. In both control and diabetic glomerular cores hyaluronan production was reduced significantly by the cyclooxygenase inhibitor indomethacin (10(-5) mol/l) [24.7 +/- 3.33 vs. 40.25 +/- 4.11 ng hyaluronan per 250 glomerular cores, p < 0.05 (control) and 36.5 +/- 6.25 vs 118.0 +/- 22.6, p < 0.01 (diabetic)]. A direct spectrophotometric microassay was used to determine the concentration of sulphated glycosaminoglycans derived from papain-digested glomerular core proteoglycans.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Insulin stimulates turnover of phosphatidylcholine in rat adipocytes.

The present study investigated the effect of insulin on phosphatidylcholine turnover in rat adipocytes labelled to equilibrium with [14C]-choline. Insulin induced a rapid turnover of this major phospholipid that was maximal by 1 min and transient in nature. Following a 1 min stimulation of the cells with insulin at a maximally effective concentration (7 nM), a 4-6% decrease in the percentage of total cellular choline associated with this phospholipid was observed. This reflected a significant transient increase in the percentage of total cellular choline associated with phosphorylcholine, which together with diacylglycerol are the phospholipase C cleavage products of phosphatidylcholine. These effects were observed over a physiological range of insulin concentrations. No effect of insulin on any other choline phospholipid or metabolite (sphingomyelin, lysophophatidylcholine, glycerophosphocholine or choline) was seen. These results suggest that insulin stimulates a phospholipase C-mediated turnover of phosphatidylcholine in rat adipocytes. The rapid nature of this turnover suggests a potential role in signal transduction.

Adipose Tissue↗
PubMed1994

Blood pressure, lipids and other risk factors for cardiovascular disease in Aborigines and persons of European descent of southeastern Australia.

Based on a survey in two country towns of southeastern Australia, cardiovascular risk-factor prevalence data from Aborigines and persons of European descent are presented. The mean diastolic blood pressure in 123 Aboriginal males was 83.2 mmHg, compared with 79.2 mmHg in 272 European males (P = 0.005). In 178 Aboriginal females, mean diastolic pressure was 79.2 mmHg, compared with 76.3 mmHg in 281 European females (P = 0.006). Mean plasma total cholesterol was higher in Europeans (both males and females: 5.7 mmol/L) than in Aborigines (in males 5.2 and females 5.0 mmol/L) (male comparison, P = 0.02, female comparison, P < 0.001). The prevalence in participants aged 25 to 64 years of at least one major risk factor (diastolic blood pressure 95 mmHg or higher, plasma cholesterol 6.5 mmol/L or higher, or smoking more than one cigarette daily) was higher in both these samples of Aborigines (94 per cent in males, 89 per cent in females) and Europeans (70 per cent in males, 59 per cent in females) than in the 1989 urban sample of the National Heart Foundation (47 per cent in males, 36 per cent in females). Multivariate analyses showed statistically significant independent contributions of body mass index and the variable 'ethnicity' (unidentified genetic and environmental differences between the groups) to blood pressure and other risk factors. The higher cardiovascular mortality of Aborigines may be explained partly by the higher prevalence of risk factors in this group compared with other Australians. Further, the risk-factor profile may be worse among rural compared with urban Europeans.

Adult↗
PubMed1993

Albuminuria in aborigines and Europids of south-eastern Australia.

OBJECTIVE: To determine the prevalence of albuminuria in Aborigines and Australians of European descent (Europids), as part of an epidemiological study of glucose intolerance and cardiovascular risk factors based in country towns of south-eastern Australia. DESIGN: Population-based cross-sectional study, with Aborigines and Europids of south-eastern Australia as the reference populations. METHOD: Random urine samples were collected from people aged > or = 35 years, and tested with Albuscreen (a test kit sensitive to urinary albumin concentrations of 0.03 g/L) and two other methods in the field. The samples were later analysed for the calculation of urinary albumin:creatinine ratios, which were then categorised according to cut-off points for abnormal renal function that have been proposed in the literature. RESULTS: Three hundred and six Aborigines and 553 Europids participated, with response rates of 90% and 94% respectively. According to Albuscreen, albuminuria was more common in Aborigines than in Europids. In men, 36% (95% confidence interval [CI], 20%-52%) of Aborigines exceeded the albumin concentration of 0.03 g/L, compared with 14% (CI, 9%-19%) of Europids (P < 0.01); in women, 39% (CI, 27%-51%) of Aborigines exceeded 0.03 g/L, compared with 18% (CI, 12%-24%) of Europids (P < 0.01). Sixty-one per cent (CI, 44%-78%) of Aboriginal men had a urinary albumin:creatinine ratio of > or = 1.30 mg/mmol, compared with 12% (CI, 7%-17%) of Europid men (P < 0.01); 56% (CI, 44%-68%) of Aboriginal women exceeded this cut-off point, compared with 23% (CI, 16%-30%) of Europid women (P < 0.01). CONCLUSION: A higher prevalence of renal disease in the Aboriginal population of south-eastern Australia is expected. Risk factors for renal disease in Aborigines throughout Australia require elucidation.

Adult↗
PubMed1993

Hyperinsulinaemia and obesity in aborigines of south-eastern Australia, with comparisons from rural and urban Europid populations.

Diabetes is more common in Aborigines than in other Australian populations, even in groups that have lived in contact with Europids for 150 years. Prevalence data on hyperinsulinaemia and obesity from urbanized south eastern Australian Aborigines are presented with Europid comparisons. Aborigines had higher mean insulin levels than Europids. In females, mean fasting insulin was 15.5 mU/l in Aborigines, compared with 9.5 mU/l in Europids (P < 0.001). The means for males were 15.1 mU/l (Aborigines) and 8.3 (Europids) (P < 0.005). Obesity was more prevalent in Aborigines. In Aboriginal females aged 25-64 years, 41/108 (38%) had BMI > 30.0, compared with 37/208 (18%) Europids (P < 0.001). In males, the difference in the prevalence of obesity in Aborigines (17/69, 25%) and Europids (34/195, 17%) was not statistically significant. Waist-hip ratio was significantly greater among Aboriginal females (mean 0.87 in persons aged 25-64 years) than among Europids (mean 0.81, P < 0.001). In males, the mean ratio in Aborigines and Europids was the same (0.94). Abdominal obesity was most prevalent among Aboriginal females. For females aged 20-49 years, 83/110 (75%) Aborigines had a waist-hip ratio > 0.80, compared with 71/165 (43%) Europids (P < 0.001). Being overweight or obese is perceived with least accuracy by Aboriginal males of the four ethnicity/gender groups. Comparisons with national data suggest a gradient in the prevalence of obesity, lowest in urban groups, more in the country, and higher still among Aborigines, which is in reciprocal order to socio-economic status. In multivariate analyses, the association of BMI with insulin was highly significant. Hyperinsulinaemia in an Aboriginal group after many years of contact with Europids may result from environmental as well as genetic influences. Relative hyperinsulinaemia is not found among those Aborigines who have developed glucose intolerance, which could be explained by earlier pancreatic exhaustion in this group.

Adolescent↗
PubMed1993

Fibronectin-induced increase in mesangial cell prostaglandin release. Effect of hyperglycemia and PKC inhibition.

Glomerular accumulation of extracellular matrix in diabetes is a potential regulator of mesangial cell-matrix interactions through transmembrane matrix receptors. We now provide evidence that PG production from rat glomerular mesangial cells is increased by Fn. An increase in PG (measured as PGE) was demonstrated in mesangial cell-enriched glomerular cores after 1-h exposure (149 +/- 8% of timed control) and was sustained over a 24-h period (214 +/- 7%). Increased PG production followed exposure to a chymotryptic fragment (120,000 M(r)) of Fn and occurred concomitant with an increase in particulate PKC activity. A tetrapeptide (Arg-Gly-Asp-Ser) with the Arg-Gly-Asp sequence, contained in Fn and the chymotryptic fragment and recognized by specific membrane receptors (integrin matrix-binding proteins), also raised PG levels. As has been shown previously, exposure to high glucose concentration can increase mesangial cell PGE production (from 677 +/- 61 pg.mg protein-1.2 h-1 at 5.6 mM glucose to 1561 +/- 132 pg.mg protein-1.2 h-1 at 50 mM glucose, P < 0.001). The response to the chymotryptic fragment of Fn also was enhanced by concurrent exposure to high glucose concentration (from 2560 +/- 199 pg.mg protein-1.2 h-1 at 5.6 mM glucose to 4672 +/- 358 pg.mg protein-1.2 h at 50 mM glucose, P < 0.001). Coincubation with H-7, an inhibitor of PKC, abolished the PG response to glucose and the chymotryptic fragment. Involvement of PKC was supported further by abrogation of the effect of chymotryptic fragment in mesangial cells cultured for a prior prolonged period with phorbol ester.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Correlation of insulin receptor level with both insulin action and breakdown of a potential insulin mediator precursor; studies in CHO cell-lines transfected with insulin receptor cDNA.

A phosphatidylinositol-glycan (PI-glycan) has been described previously that may serve as the precursor for a mediator of some of insulins actions. The present study further addresses the potential relevance of this compound by correlating its breakdown with other insulin actions in Chinese hamster ovary (CHO) cells which express different levels of insulin receptor. Comparisons were drawn between parent CHO cells expressing 3 x 10(3) receptors/cells and two cell-lines transfected with human insulin receptor cDNA, that expressed 600 (CHO.TH) and 300 (CHO.T) times the parent receptor level. A PI-glycan was isolated from all cells that incorporated [3H]glucosamine, [3H]galactose and [3H]inositol and was rapidly turned over upon insulin stimulation. Maximal turnover by insulin of approx. 20% was achieved in each cell line consistent with the fibroblastic nature of these cells. The effect of increased insulin receptor expression was to increase the sensitivity of the PI-glycan response to insulin. Increasing receptor number from 3 x 10(3) to 0.88 x 10(6) also increased the sensitivity of response of other insulin actions measured in this study, namely activation of pyruvate dehydrogenase (PDH), glucose utilization and transport. Thus turnover of the PI-glycan is linked closely to both metabolic actions of insulin and to cell surface insulin receptor expression further supporting its potential role in insulin action.

Animals↗
PubMed1992

The link between hyperglycaemia and diabetic nephropathy.

A large number of experimental studies in animals and retrospective or non-randomised prospective studies in humans provide support for the concept that the microvascular complications of diabetes mellitus are dependent on hyperglycaemia. This review focuses on four potential biochemical pathways linking hyperglycaemia to changes within the kidney which can plausibly be linked to the functional and structural changes characterising diabetic nephropathy. These four pathways are the polyol pathway, non-enzymatic glycation, glucose autoxidation and de novo synthesis of diacylglycerol leading to protein kinase C and phospholipase A2 activation. Rather than being independent, there are several potential interactions between these four pathways which may explain confusing and overlapping effects observed in studies examining inhibitors of individual pathways. As many of the steps which follow on glucose metabolism are subject to modification by dietary and pharmacological means, the further delineation of the pathogenetic sequence leading to tissue damage in diabetes should allow a logical and effective approach to the prevention or treatment of the complications of diabetes.

Aldehyde Reductase↗
PubMed1992

The effects of low density lipoprotein and high density lipoprotein on phosphoinositide hydrolysis in bovine aortic endothelial cells.

Low density lipoprotein (LDL) and high density lipoprotein (HDL3) were tested for their ability to induce inositol phospholipid turnover and inositol phosphate production in bovine aortic endothelial cells (BAEC). The production of inositol phosphates following hydrolysis of the phosphoinositides was demonstrated by two methods; release of [3H]inositol phosphates after labelling with [3H]myo-inositol and by a direct binding assay for inositol 1,4,5-trisphosphate (InsP3). Acute exposure to LDL induced InsP3 release at low concentrations of the lipoprotein within the physiological range of LDL in tissues. HDL3 did not cause any release of the inositol phosphates. Pre-incubation of BAEC with HDL3 suppressed bradykinin- and LDL-induced inositol phosphate production in BAEC in a concentration-dependent manner. It is concluded that LDL acutely stimulates phosphoinositide breakdown and that pre-incubation of cells with HDL3 inhibits this effect. The mechanism responsible for these effects remains to be elucidated.

Animals↗
PubMed1992

The prevalence of glucose intolerance in aborigines and Europids of south-eastern Australia.

Based on oral glucose tolerance testing, the prevalence of diabetes in Australian adults has ranged from 2.3% in Europids in 1966 to 20% in small surveys of Aborigines. We have surveyed Aborigines and Europids simultaneously for further comparison of diabetes prevalence between these population groups. The samples were drawn from two adjacent country towns in south-eastern Australia, where Aborigines and Europids have been in contact for 150 years. By the 2-h (post-75 g oral glucose load) criterion (venous plasma glucose greater than or equal to 11.1 mmol/l), the crude prevalence of diabetes among 306 Aborigines was 7.8%, significantly higher than the 3.4% among 553 Europids (P less than 0.01). The prevalence of impaired glucose tolerance was similar in both groups (6.9% in Aborigines, 6.0% in Europids, no significant difference). Adjustment for the marked differences in age distribution between Aborigines and Europids by direct standardization to the 1980 world population increased the apparent differences, with the finding of a four-fold greater prevalence among Aborigines (8.1% compared with 1.9%). The greater frequency of glucose intolerance among Aborigines appears to persist despite the higher proportion of Europid genetic mix with these urbanized south-eastern groups than with Aborigines from remote settings.

Adult↗
PubMed1992

Smoking in aborigines and persons of European descent in southeastern Australia: prevalence and associations with food habits, body fat distribution and other cardiovascular risk factors.

As part of a population-base study of risk factors for heart disease, we aimed to establish the prevalence of smoking and to identify associations between smoking and other risk factors in Australian Aborigines (n = 306) and persons of European descent (n = 553) in two country towns. Smoking prevalence was first analysed as a dichotomy (current smokers compared with nonsmokers), and according to three levels of exposure (< 10, 10-20 and > 20 cigarettes per day), and two levels of nonexposure (never and former smoker). Other behavioural, biochemical and physical variables were included in multivariable analyses. Of the Aborigines, 64.4 per cent (95 per cent confidence interval (CI) 59.0 per cent to 69.8 per cent) were current cigarette smokers, compared with 22.8 per cent of non-Aborigines (CI 19.3 per cent to 26.3 per cent). For persons aged 13 to 54 years, using the five categories of exposure, smoking in Aborigines again far exceeded that in non-Aborigines in all age groups (for males chi 2 = 72.8, for females chi 2 = 94.6, 4 df, P = < 0.0001 for both sexes). In non-Aboriginal females, the highest prevalence was in the youngest group (56 per cent of those aged 13 to 17 years). Food habit was associated with smoking. Subjects who ate meat without trimming the fat were more likely to smoke. In Australian country towns, Aborigines and all young women need smoking cessation programs. The nutritional status of smokers requires further study.

Adolescent↗
PubMed1991

The effect of aldose reductase inhibitors on glomerular prostaglandin production and urinary albumin excretion in experimental diabetes mellitus.

The effect of two structurally unrelated aldose reductase inhibitors, sorbinil and ponalrestat, on glomerular prostaglandin production and urinary albumin excretion was investigated in rats with diabetes induced by streptozotocin. It was found that both aldose reductase inhibitors, when administered from the time of induction of the diabetes, significantly decreased the raised urinary albumin excretion in the diabetic rats, although it remained elevated compared with non-diabetic rats. Glomerular prostaglandin E and 6-keto-prostaglandin F1 alpha production was significantly increased in glomeruli obtained from the diabetic rats. Inhibition of aldose reductase caused a reduction in the raised glomerular prostaglandin production, although this remained above that observed in the non-diabetic rats. Subsequent experiments were performed to determine whether the effects of the aldose reductase inhibitors could be explained by effects on glomerular filtration rate. It was found that ponalrestat, at a dose which markedly reduced urinary albumin excretion, did not significantly affect glomerular filtration rate in non-diabetic rats, rats with untreated streptozotocin-induced diabetes and rats with diabetes partially treated with low dose insulin. Glomerular sorbitol concentrations were significantly elevated in untreated diabetic rats as early as two weeks after the induction of diabetes. It is concluded that the administration of aldose reductase inhibitors from the time of induction of diabetes significantly reduces glomerular prostaglandin production and urinary albumin excretion. The latter effect is not due to an effect on glomerular filtration rate. Increased polyol pathway activity may account in part for the increased glomerular prostaglandin production and urinary albumin excretion in early experimental diabetes.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Stimulation by human chorionic gonadotropin of prostaglandin synthesis by early human placental tissue.

Successful establishment of pregnancy is dependent on inhibition of clotting and suppression of the maternal immune response at the feto-maternal interface. Early human placental production of prostacyclin (PGI2) and prostaglandin E2 (PGE2) may be important in this process. To examine the possible role of these PGs, we studied PGE and 6-keto-PGF1 alpha (stable metabolite of PGI2) synthesis in human placental (9-17 weeks gestation) organ cultures, and monolayer cultures of purified trophoblasts. PGE2 appeared to be the major protanoid formed. Other arachidonic acid metabolites identified in placental organ culture were 6-keto-PGF1 alpha, thromboxane B2, PGF2 alpha, leukotriene B4, 5(S)-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, and 15-HETE. The synthesis of PGE and 6-keto-PGF1 alpha altered with gestation and was maximal in the younger placentas. Arachidonic acid (33 microM) stimulated and indomethacin (28 microM) inhibited PG production. hCG, including physiological concentrations, stimulated PGE and 6-keto-PGF1 alpha synthesis in placental organ cultures. This effect was most striking in the 9-12 week placentas, compared to 15-17 week placentas. A similar hCG-induced stimulation of PGE production occurred in monolayer cultures of trophoblasts. The addition of TSH, FSH, and LH indicated that this effect was specific for hCG. These data suggest that hCG may have a biological role in the regulation of PG synthesis in early human placenta.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Increased secretion of insulin-like growth factor-binding proteins and decreased secretion of insulin-like growth factor-II by muscle from growth-retarded neonatal rats.

Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) may be important factors in the control of neonatal growth. We have examined the production, in vitro, of IGFBPs and IGFs by hind-limb skeletal muscle from normal and small-for-gestational age (SGA) neonatal rats. Conditioned medium was collected from muscle strips after incubation at 37 degrees C for 2 h in Ham's F-12 medium. The conditioned medium was subjected to acid-gel permeation chromatography to separate IGFBPs from IGFs. The binding of 125I-labelled IGF-I to IGFBPs from both control and SGA muscle was displaced equipotently by IGF-I and IGF-II and not at all by insulin. IGFBPs from control and SGA muscles bound IGF-I with comparable affinities (Kd = 0.071 and 0.069 nmol/l respectively). When IGF-II was used as tracer, neither IGF-I nor insulin competed for binding. Western ligand blots of IGFBPs in conditioned media from both control and SGA muscles showed three bands of radioactivity at molecular masses equivalent to 24, 30 and 40 kDa. When the release of IGFBPs by muscle tissue in vitro was quantified by measuring the number of IGF-I binding sites in acid-fractionated medium it was apparent that the muscles from SGA pups secreted significantly more IGFBPs (39.3 +/- 7.5 fmol/mg muscle protein per 2 h) than the muscles from control pups (17.8 +/- 2.7 fmol/mg protein per 2 h; P less than 0.05). In contrast to the IGFBPs, more IGF activity was secreted by the muscles from the control pups (61.1 +/- 15.6 fmol/mg muscle protein per 2 h) than the muscles from the SGA pups (12.6 +/- 5.8 fmol/mg muscle protein per 2 h; P less than 0.05). Analysis of the IGF activity with assays specific for IGF-I and IGF-II showed that both SGA and control muscles secreted predominantly IGF-II with approximately 10% of the total IGF activity measurable as IGF-I. This differential secretion of IGFBPs and IGFs may be associated with the reduced growth potential of the SGA neonate.

Animals↗
PubMed1991

Evolution of insulin resistance in New Zealand obese mice.

The etiology of non-insulin-dependent diabetes mellitus (NIDDM) is not known. Hyperglycemia is due to increased hepatic glucose production (HGP), decreased glucose uptake, and impaired insulin secretion. It is unknown if these defects are coinherited or if one precedes and causes the others. The aim of this study was to determine the earliest defects in the evolution of the syndrome in the New Zealand obese (NZO) mouse, a polygenic model of NIDDM. NZO and control NZC mice were studied at 4-5 and 20 wk of age. Glucose turnover and glucose uptake in individual tissues were measured basally and during a hyperinsulinemic clamp. First-phase insulin secretion was measured after an intravenous glucose load. HGP was higher in the NZO mice both basally and during the clamp at both ages. At 4-5 wk of age, there was evidence of insulin insensitivity in brown adipose tissue, soleus, diaphragm, red quadriceps, and red gastrocnemius but not in heart, white quadriceps, and white gastrocnemius. In 20-wk-old mice, insulin responsiveness was decreased in white and brown adipose tissue and soleus muscle but not in heart, diaphragm, red and white quadriceps, and red and white gastrocnemius. First-phase insulin secretion (percentage rise above basal) 3 min after the glucose bolus was impaired in NZO mice at both ages. We conclude that hepatic glucose overproduction, brown adipose tissue and skeletal muscle insulin resistance, and impaired first-phase insulin secretion are all early abnormalities in the NZO mouse.

Adipose Tissue↗
PubMed1990

Insulin-dependent contractility of glomerular mesangial cells in response to angiotensin II, platelet-activating factor and endothelin is attenuated by prostaglandin E2.

Culture of glomerular mesangial cells in the absence of insulin decreased the degree of contraction of individual cells in response to vasoconstrictive agonists, angiotensin II, platelet-activating factor and endothelin 1, as compared with cells cultured in the presence of insulin (0.7 nM). This change was associated with a decreased sensitivity of the intracellular Ca2+ response to vasoactive agents in fura-2-loaded cells and with an increase in the basal level of prostanoid [prostaglandins (PG) E1 and E2] production estimated by radioimmunoassay. Addition of exogenous PGE2 to insulin-exposed cells decreased the contractile response to that observed in insulin-deficient cells. Inclusion of 8-bromo cyclic AMP had a similar effect. In 45Ca2(+)-release studies it was shown that, in saponin-permeabilized insulin-exposed cells, preincubation with exogenous PGE2 or 8-bromo cyclic AMP decreased the sensitivity of 45Ca2+ release in response to Ins(1,4,5)P3, as demonstrated by an increase in the EC50 (concn. giving half-maximal effect) to 0.182 +/- 0.024 microM and 0.457 +/- 0.031 microM respectively, as compared with untreated permeabilized cells (EC50 0.091 +/- 0.021 microM). A similar decrease in Ins(1,4,5)P3-sensitive 45Ca2+ release was seen in permeabilized cells from insulin-free conditions of culture (EC50 0.20 +/- 0.061 microM). As altered glomerular haemodynamics are found in insulinopaenic diabetic conditions, it is proposed that a decrease in intracellular Ca2+ availability in response to vasoactive agonists and consequent decrease in mesangial-cell contractility contributes to the hyperfiltration seen in this condition.

8-Bromo Cyclic Adenosine Monophosphate↗