EFFECTS OF PREGNANCY IN THE RAT ON THE SIZE AND INSULIN SECRETORY RESPONSE OF THE ISLETS OF LANGERHANS

1972 ◽  
Vol 54 (2) ◽  
pp. 317-325 ◽  
Author(s):  
I. C. GREEN ◽  
K. W. TAYLOR

SUMMARY The secretory response of rat islets of Langerhans was examined during pregnancy and compared with insulin release in normal rat islets. The threshold for a secretory response to glucose was lowered for islets from pregnant rats by comparison with non-pregnant controls. In addition, such islets showed a greatly increased sensitivity to glucose concentrations over the range 3·5–20 mmol/1. Significantly lower fasting blood glucose levels were found in pregnant rats in vivo, compared with controls. Insulin secretagogues other than glucose were tested for their effects on islets during pregnancy. Despite the high baseline of insulin secretion in response to glucose in pregnancy, there was an additional increased secretory response to arginine and theophylline. In contrast to their response to glucose, pregnant rat islets did not display an increased sensitivity to leucine. Glucagon, while it increased the insulin response of normal islets, had no significant effect on increasing the insulin response from pregnant rat islets suggesting that adenyl cyclase activity is already highly stimulated in pregnancy. In addition, the insulin, DNA and protein content of islets during pregnancy were increased significantly above normal values. The results suggested that rat islets are not only larger in pregnancy, but that they possess a more sensitive mechanism for detecting and responding to glucose and other secretagogues.

1974 ◽  
Vol 62 (1) ◽  
pp. 137-143 ◽  
Author(s):  
I. C. GREEN ◽  
K. W. TAYLOR

SUMMARY The effects of diet on the altered insulin secretory responses of islets of Langerhans of pregnant rats have been investigated. The daily food intake of pregnant rats was found to exceed that of control non-pregnant rats by 20% on average. Depriving pregnant rats of this additional food resulted in an alteration in the pattern of insulin secretion seen in pregnancy, such that the sensitivity to stimulation by low glucose concentrations was abolished. The contribution made by different components of the diet to the secretory response in pregnancy was investigated. When additional carbohydrate, though not protein, was fed to pregnant rats on a restricted food intake, the sensitivity of the islets to glucose stimulation was restored. It was concluded that the quantity and in particular the carbohydrate content of food eaten by pregnant rats exerts an important influence on the changes in insulin secretion in pregnancy.


1977 ◽  
Vol 166 (3) ◽  
pp. 501-507 ◽  
Author(s):  
Adrian J. Bone ◽  
Simon L. Howell

1. Insulin biosynthesis in isolated rat islets of Langerhans was determined by the incorporation of [3H]leucine into newly synthesized islet proteins. Anti-insulin serum covalently coupled to a solid phase (CNBr-activated Sepharose 4B) was used to separate the immunoreactive proinsulin and insulin from other islet proteins. This method was applied to a study of the regulation of insulin biosynthesis in isolated rat islets of Langerhans during pregnancy, and immediately after a period of food deprivation. 2. Islets isolated from pregnant rats showed an increased basal rate of synthesis compared with the non-pregnant controls. In addition, they showed a significant increase in biosynthesis of proinsulin and insulin in comparison with the normal islets over a range of glucose concentrations of 2–20mm. 3. Addition of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine significantly increased the insulin-synthetic response of normal islets over the glucose range 5–20mm, so that their glucose response approached that of islets from pregnant rats. 4. Normal female rates were injected with a long-acting progesterone derivative (hydroxyprogesterone hexanoate), to investigate the role of progesterone on the increased insulin biosynthesis observed in islets in pregnancy. There appeared to be no marked difference in insulin biosynthesis between the islets from the progesterone-injected and control rats in the presence of 2mm- or 6mm-glucose alone. However, in the presence of 4mm- or 6mm-glucose and 3-isobutyl-1-methylxanthine there was a significant increase in insulin biosynthesis in the progesterone-treated animals. 5. Total islet protein biosynthesis was determined by the incorporation of [3H]leucine into trichloroacetic acid-precipitable islet proteins. Islets isolated from normal rats showed a 1.6-fold increase in incorporation over the glucose concentration range 2–20mm, and this value remained unchanged during starvation; however, rates of incorporation were significantly raised in islets isolated from pregnant rats in the presence of 20mm-glucose. 6. Islets from starved and fed control rats were incubated in the presence of increasing concentrations of glucose or glucose+3-isobutyl-1-methylxanthine. The islets isolated from the starved animals showed a diminished insulin-synthetic response to glucose as compared with the controls; this response was partially restored to normal values by elevation of cyclic AMP concentrations by using 3-isobutyl-1-methylxanthine. 7. It is suggested that the alterations in glucose-stimulated insulin biosynthesis observed in islets during pregnancy and after a period of starvation could be attributable, at least in part, to a long-term alteration of the cyclic AMP system, and in pregnancy to a direct or indirect effect of progesterone on β-cell function.


1972 ◽  
Vol 20 (11) ◽  
pp. 873-879 ◽  
Author(s):  
S. L. HOWELL ◽  
MARGARET WHITFIELD

A cytochemical method has been used to investigate the localization of adenyl cyclase activity in A and B cells of isolated rat islets of Langerhans. Adenosine triphosphate was initially utilized as substrate, the pyrophosphate liberated being precipitated by lead ions at its site of production. The specificity of the method was increased by the use of adenylyl-imidodiphosphate as an alternative substrate; this adenosine triphosphate analogue was not hydrolyzed by adenosine triphosphatase but provided an effective substrate for adenyl cyclase. Adenyl cyclase activity, which was found to retain its glucagon and fluoride sensitivity in glutaraldehyde-fixed tissue, was found exclusively and almost uniformly in the plasma membranes of A and B cells. Storage granule membrane, incorporated into the plasma membrane during secretion of the granule content by exocytosis, appeared to be devoid of adenyl cyclase activity.


2002 ◽  
Vol 283 (3) ◽  
pp. G757-G766 ◽  
Author(s):  
Jingsong Cao ◽  
Bruno Stieger ◽  
Peter J. Meier ◽  
Mary Vore

The expression of hepatic multidrug resistance-associated protein (Mrp)1, 2, 3, and 6 and organic anion transporting polypeptides (Oatp)1 and 2 were examined in control and 20- to 21-day pregnant rats. Western analysis showed that expression of Oatp2 was decreased 50% in pregnancy, whereas expression of Oatp1 did not change. Expression of Mrp2 protein determined by Western analysis of total liver homogenate decreased to 50% of control levels in pregnant rats, consistent with studies using plasma membranes. Confocal immunohistochemistry showed that Mrp2 expression was confined to the canalicular membrane in both control and pregnant rats and was not detectable in intracellular compartments. In isolated perfused liver, the biliary excretion of 2,4-dintrophenyl-glutathione was significantly decreased in pregnancy, consistent with decreased expression of Mrp2. The expression of the basolateral transporter Mrp1 was not altered in pregnancy, whereas expression of Mrp6 mRNA was decreased by 60%. Expression of Mrp3 was also decreased by 50% in pregnant rat liver, indicating differential regulation of Mrp isoforms in pregnancy. These data also demonstrate that decreased Mrp2 expression is not necessarily accompanied by increased Mrp3 expression.


1973 ◽  
Vol 134 (2) ◽  
pp. 481-487 ◽  
Author(s):  
I. C. Green ◽  
S. L. Howell ◽  
W. Montague ◽  
K. W. Taylor

1. The concentrations of cyclic AMP were compared in islets of Langerhans isolated from the pancreases of normal female and pregnant rats and were higher in islets in pregnancy. 2. There was also a significant increase in adenylate cyclase activity in homogenates of islets from pregnant rats compared with those from normal rats. 3. Increased cyclic AMP concentration in islets from pregnant rats was reflected in increased protein kinase activity. When the cyclic AMP-dependent protein kinase activity was increased by 3-isobutyl-1-methylxanthine this stimulated activity was significantly greater in pregnancy. 4. Insulin-secretion studies with islets from normal and pregnant rats showed that theophylline or 3-isobutyl-1-methylxanthine, which raise intracellular cyclic AMP concentrations, caused a significantly greater insulin secretion in pregnancy. 5. It was also found that in the presence of a glucose concentration too low to stimulate insulin secretion, the latter could be induced if the cyclic AMP concentrations were raised sufficiently with 3-isobutyl-1-methylxanthine. 6. It is suggested that the higher cyclic AMP concentrations observed in islets in pregnancy mediate the greater insulin-secretory capacity, as well as the greater sensitivity of these islets to low glucose concentrations.


Medicines ◽  
2021 ◽  
Vol 8 (12) ◽  
pp. 79
Author(s):  
Peter Uchenna Amadi ◽  
Emmanuel Nnabugwu Agomuo ◽  
Chinyere Nneka Ukaga ◽  
Uche Chinedu Njoku ◽  
Joy Adaku Amadi ◽  
...  

Background: Most pregnant women living in high malaria endemic regions of Nigeria use herbal remedies for the management of malaria-in-pregnancy, rather than the commonly prescribed drugs. Remedies common to this area involve a suspension of A. indica (AI) leaves and in some cases, a suspension containing a mixture of AI and D.edulis (PS). Aim: This study examined the therapeutic efficacies of AI, PS, or a combination of AI and PS in a pregnant rat model for exoerythrocytic stages of Plasmodium falciparum parasite. Method: A predetermined sample size of 30 dams was used (for a power level and confidence interval of 95%), and divided equally into six groups made up of non-malarous dams, untreated malarous dams, and malarous dams either treated exclusively with 1 mL of 3000 mg/kg b.w AI, 1000 mg/kg b.w PS, AI + PS (50% v/v), or 25 mg/kg b.w CQ. Result: No maternal mortality was recorded. AI significantly improved maternal weight gain from 32.4 to 82.2 g and placental weight from 0.44 to 0.53 g. In the curative test, AI and AI + PS significantly reduced the average percentage parasitemia (APP) in the pregnant rats from >80% to <20%. No significant difference in the APP was found between the pregnant rats treated with any of CQ or AI during the suppressive test. Results for the prophylactic test of the study groups showed that the APP was significantly reduced from 24.69% to 3.90% when treated with AI and 3.67% when combined with PS. AI + PS reduced diastolic blood pressure from 89.0 to 81.0 mm/Hg and compared with that of the non malarous dams. AI or AI + PS significantly increased the platelet counts (103 µL) from 214.1 to 364.5 and 351.2, respectively. AI and AI + PS improved birth weight from 2.5 to 3.9 g and crown rump length from 2.6 to 4.1 cm. For biomarkers of preeclampsia, combining AI and PS led to the reversal of the altered levels of creatine kinase, lactate dehydrogenase, cardiac troponin, soluble Fms-Like Tyrosine Kinase-1, and placental growth factor. Conclusions: This study validates the use of A. indica for the treatment of gestational malaria due to its antiplasmodial and related therapeutic effects and in combination with pear seeds for the management of malaria-in-pregnancy-induced preeclampsia.


Author(s):  
Gondo H. K. ◽  
Kusworini H. ◽  
Arsana W. ◽  
Sardjono W.

Preeclampsia/eclampsia (PEE) was the main cause of death in pregnancy. However, until now, this disease has no adequate medical prevention for lack of its basic molecular pathomechanism. In recent years, there are growing number of study has concern trophoblast apoptosis as important trigger. Thropoblast apoptosis has been shown in many report lead to trophoblast failure to invade into endometrial tissue. Invasion failure of trophoblast was characterized with high expression of IL-17 in its tissue. Spirulina arthrospira plant or also called blue-green algae has been consumed since by the Aztec tribe. Several studies have proven that this plant have the immunomodulation properties stimulate various immune functions such as production of cytokines, chemokines and other anti-inflammatory mediators. Its active bioactive Phycocyanin (PC) has been shown have an effect as anti-inflammatory and antioxidant. Previous study has been shown that this substance has beneficial effect in preeclampsia inhibition in rat models via its inflammatory reducing effect However, there are lack of information concerning its role in trophoblast IL-17. Hence, this study is conduct to reveal its role in IL-17 expression in trophoblast in preeclampsia. Methods. This research used animal models with PE/E pregnant rat. PE/E induced by IL-6 intravein at dose 5 ng/100 g/day body weight. Animals divided in 6 groups of treatment with two groups control and four groups of PC treatment in different dose. After decapitated, uterus tissue processed to view its IL-17 expression using immunofluoresnce Result. This study has proven IL-17 reducing effect of PC in preeclampsia model of pregnant rats induced by IL -6. PC has reducing IL-17 expression significantly in trophoblast tissue of pregnant rats models induced by IL-6 at dose of 40 ng/100 kg weight. Conclusion. This study confirm that PC has a protective effect on pregnant rats preeclampsia through its inhibiton of trophoblast IL-17.


Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1626-1637 ◽  
Author(s):  
Shuaike Ma ◽  
Michael J. Shipston ◽  
David Morilak ◽  
John A. Russell

We sought to explain decreased ACTH secretory responses to stress in pregnant rats by investigating hypothalamic CRH and vasopressin secretion and actions on anterior pituitary corticotrophs. In late pregnancy median eminence, CRH content was reduced (by 12%). Anterior pituitary proopiomelanocortin mRNA expression, measured by in situ hybridization but not radioimmunoassayed ACTH content, was also reduced (by 45% on d 21); CRH receptor (CRHR)1 mRNA expression was unaltered in pregnancy, but V1b receptor mRNA expression was reduced (by 19%). ACTH secretory responses, measured in jugular blood, to CRH (200 ng/kg iv) or vasopressin (1.7 μg/kg, iv) were reduced on d 21 vs. virgins (49% and 44%), but the response to combined CRH and vasopressin injection was intact. Either antalarmin (CRHR1 antagonist; 20 mg/kg ip) or dP(Tyr(Me)2),Arg-NH29)AVP (V1a/b antagonist; 10 μg/kg, iv) pretreatment reduced the ACTH secretory response to forced swimming (90 sec) in virgin rats (by 57% and 40%), but only antalarmin was effective in pregnant rats (53% decrease). In vitro, measuring ACTH secretion from acutely dispersed anterior pituitary cells showed increased corticotroph sensitivity in pregnancy to CRH and to CRH augmentation by vasopressin, attributable to increased intracellular cAMP action. Hence, in late pregnancy, reduced anterior pituitary CRHR1 or V1b receptor expression did not impair corticotroph responses to CRH or vasopressin. Rather, diminished secretagogue secretion in vivo accounts for reduced action of stress levels of exogenous CRH or vasopressin alone; the late pregnancy attenuated ACTH secretory response to swim stress is deduced to be due to reduced vasopressin release by parvocellular paraventricular nuclei neurones.


2015 ◽  
Vol 309 (1) ◽  
pp. F63-F70 ◽  
Author(s):  
Crystal A. West ◽  
Alicia A. McDonough ◽  
Shyama M. E. Masilamani ◽  
Jill W. Verlander ◽  
Chris Baylis

Pregnancy is characterized by plasma volume expansion due to Na+ retention, driven by aldosterone. The aldosterone-responsive epithelial Na+ channel is activated in the kidney in pregnancy. In the present study, we investigated the aldosterone-responsive Na+-Cl− cotransporter (NCC) in mid- and late pregnant rats compared with virgin rats. We determined the abundance of total NCC, phosphorylated NCC (pNCC; pT53, pS71 and pS89), phosphorylated STE20/SPS-1-related proline-alanine-rich protein kinase (pSPAK; pS373), and phosphorylated oxidative stress-related kinase (pOSR1; pS325) in the kidney cortex. We also measured mRNA expression of NCC and members of the SPAK/NCC regulatory kinase network, serum and glucocorticoid-regulated kinase (SGK)1, total with no lysine kinase (WNK)1, WNK3, and WNK4. Additionally, we performed immunohistochemistry for NCC kidneys from virgin and pregnant rats. Total NCC, pNCC, and pSPAK/OSR1 abundance were unchanged in midpregnant versus virgin rats. In late pregnant versus virgin rats, total NCC and pNCC were decreased; however, pSPAK/OSR1 was unchanged. We detected no differences in mRNA expression of NCC, SGK1, total WNK1, WNK3, and WNK4. By immunohistochemistry, NCC was mainly localized to the apical region in virgin rats, and density in the apical region was reduced in late pregnancy. Therefore, despite high circulating aldosterone levels in pregnancy, the aldosterone-responsive transporter NCC is not increased in total or activated (phosphorylated) abundance or in apical localization in midpregnant rats, and all are reduced in late pregnancy. This contrasts to the mineralocorticoid-mediated activation of the epithelial Na+ channel, which we have previously reported. Why and how NCC escapes aldosterone activation in pregnancy is not clear but may relate to regional differences in aldosterone sensitivity the increased K+ intake or other undefined mechanisms.


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