scholarly journals Strain-Dependent Influences on the Hypothalamo-Pituitary-Adrenal Axis Profoundly Affect the 7B2 and PC2 Null Phenotypes

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3438-3444 ◽  
Author(s):  
Juan R. Peinado ◽  
Virginie Laurent ◽  
Sang-Nam Lee ◽  
Bonnie W. Peng ◽  
John E. Pintar ◽  
...  
Keyword(s):  
Null Mouse ◽  
Wild Type ◽  
Acth Stimulation ◽  
Phenotypic Differences ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Phenotype Characteristic ◽  
Strain Dependent ◽  
Pituitary Adrenal Axis

Abstract Two null mouse models have previously been created to study the role of the prohormone convertase (PC2) and its helper protein 7B2; unexpectedly, the phenotypes of these two nulls differ profoundly, with the 7B2 but not the PC2 null dying at 5 wk. The genetic backgrounds of these two models differ, with the 7B2 null in a 129/SvEv (129) background and the PC2 null in a mixed C57BL/N6:129/SvEv (B6:129) background. Because background can contribute greatly to phenotype, we have here examined strain influence on the hypothalamo-pituitary-adrenal (HPA) axis and glucose levels in wild-type, 7B2 null, and PC2 null mice. Wild-type B6 and 129 mice differed in basal corticosterone and glucose levels. When 7B2 nulls were transferred onto the B6 background, they survived and showed greatly decreased circulating corticosterone and increased blood glucose levels, most likely due to the comparatively higher adrenal resistance of the B6 strain to ACTH stimulation. Circulating ACTH levels were increased over wild-type in the B6 7B2 null but did not reach levels as high as the 129 7B2 null. Conversely, when the mixed-strain PC2 nulls were bred into the 129 background at the N6 generation, they began to exhibit the Cushing’s-like phenotype characteristic of 129 7B2 null mice and died before 6 wk of age. Taken together, these results indicate that background effects are critical because they increase the phenotypic differences between the 7B2 and PC2 nulls and play a life-or-death role in the ACTH hypersecretion syndrome present in both 129 nulls.

scholarly journals Progressive development of insulin resistance phenotype in male mice with complete aromatase (CYP19) deficiency

2003 ◽  
Vol 176 (2) ◽  
pp. 237-246 ◽  
Author(s):  
K Takeda ◽  
K Toda ◽  
T Saibara ◽  
M Nakagawa ◽  
K Saika ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Serum Triglyceride ◽  
Male Mice ◽  
Wild Type ◽  
Glucose Levels ◽  
Cholesterol Levels ◽  
Blood Glucose Levels ◽  
Body Weights

Aromatase (CYP19) is a cytochrome P450 enzyme that catalyzes the formation of aromatic C18 estrogens from C19 androgens. It is expressed in various tissues and contributes to sex-specific differences in cellular metabolism. We have generated aromatase-knockout (ArKO) mice in order to study the role of estrogen in the regulation of glucose metabolism. The mean body weights of male ArKO (-/-) mice (n=7) and wild-type littermates (+/+) (n=7) at 10 and 12 weeks of age were 26.7+/-1.9 g vs 26.1+/-0.8 g and 28.8+/-1.4 g vs 26.9+/-1.0 g respectively. The body weights of the ArKO and wild-type mice diverged between 10 and 12 weeks of age with the ArKO males weighing significantly more than their wild-type littermates (P<0.05). The ArKO males showed significantly higher blood glucose levels during an intraperitoneal glucose tolerance test compared with wild-type littermates beginning at 18 weeks of age. By 24 weeks of age, they had higher fasting blood glucose levels compared with wild-type littermates (133.8+/-22.8 mg/dl vs 87.8+/-20.3 mg/dl respectively; P<0.01). An intraperitoneal injection of insulin (0.75 mU insulin/g) caused a continuous decline in blood glucose levels in wild-type mice whereas ArKO males at 18 weeks and older exhibited a rebound increase in glucose levels 30 min after insulin injection. Thus, ArKO male mice appear to develop glucose intolerance and insulin resistance in an age-dependent manner. There was no difference in fasting serum triglyceride and total cholesterol levels between ArKO male mice and wild-type littermates at 13 and 25 weeks of age. However, serum triglyceride and cholesterol levels were significantly elevated following a meal in ArKO mice at 36 weeks of age. Serum testosterone levels in ArKO male mice were continuously higher compared with wild-type littermates. Treatment of ArKO males with 17beta-estradiol improved the glucose response as measured by intraperitoneal glucose and insulin tolerance tests. Treatment with fibrates and thiazolidinediones also led to an improvement in insulin resistance and reduced androgen levels. As complete aromatase deficiency in man is associated with insulin resistance, obesity and hyperlipidemia, the ArKO mouse may be a useful animal model for examining the role of estrogens in the control of glucose and lipid homeostasis.

scholarly journals Role of Insulin in Health and Disease: An Update

2021 ◽  
Vol 22 (12) ◽  
pp. 6403
Author(s):  
Md Saidur Rahman ◽  
Khandkar Shaharina Hossain ◽  
Sharnali Das ◽  
Sushmita Kundu ◽  
Elikanah Olusayo Adegoke ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Basic Research ◽  
Future Research ◽  
Protective Effects ◽  
Glucose Levels ◽  
Physiological Processes ◽  
Blood Glucose Levels ◽  
Wide Range ◽  
Health And Disease

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.

scholarly journals Role of Melanocortin Signaling in Neuroendocrine and Metabolic Actions of Leptin in Male Rats With Uncontrolled Diabetes

Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4157-4167 ◽  
Author(s):  
Thomas H. Meek ◽  
Miles E. Matsen ◽  
Vincent Damian ◽  
Alex Cubelo ◽  
Streamson C. Chua ◽  
...  
Keyword(s):  
Male Rats ◽  
Melanocortin Receptor ◽  
Glucose Lowering ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Uncontrolled Diabetes ◽  
Streptozotocin Induced Diabetes ◽  
Melanocortin Signaling ◽  
Antidiabetic Effects

Abstract Although the antidiabetic effects of leptin require intact neuronal melanocortin signaling in rodents with uncontrolled diabetes (uDM), increased melanocortin signaling is not sufficient to mimic leptin's glucose-lowering effects. The current studies were undertaken to clarify the role of melanocortin signaling in leptin's ability to correct metabolic and neuroendocrine disturbances associated with uDM. To accomplish this, bilateral cannulae were implanted in the lateral ventricle of rats with streptozotocin-induced diabetes, and leptin was coinfused with varying doses of the melanocortin 3/4 receptor (MC3/4R) antagonist, SHU9119. An additional cohort of streptozotocin-induced diabetes rats received intracerebroventricular administration of either the MC3/4R agonist, melanotan-II, or its vehicle. Consistent with previous findings, leptin's glucose-lowering effects were blocked by intracerebroventricular SHU9119. In contrast, leptin-mediated suppression of hyperglucagonemia involves both melanocortin dependent and independent mechanisms, and the degree of glucagon inhibition was associated with reduced plasma ketone body levels. Increased central nervous system melanocortin signaling alone fails to mimic leptin's ability to correct any of the metabolic or neuroendocrine disturbances associated with uDM. Moreover, the inability of increased melanocortin signaling to lower diabetic hyperglycemia does not appear to be secondary to release of the endogenous MC3/4R inverse agonist, Agouti-related peptide (AgRP), because AgRP knockout mice did not show increased susceptibility to the antidiabetic effects of increased MC3/4R signaling. Overall, these data suggest that 1) AgRP is not a major driver of diabetic hyperglycemia, 2) mechanisms independent of melanocortin signaling contribute to leptin's antidiabetic effects, and 3) melanocortin receptor blockade dissociates leptin's glucose-lowering effect from its action on other features of uDM, including reversal of hyperglucagonemia and ketosis, suggesting that brain control of ketosis, but not blood glucose levels, is glucagon dependent.

A GLP-1 Receptor Agonist Inhibits Aldosterone Release in Healthy Volunteers

2021 ◽  
Vol 53 (06) ◽  
pp. 402-407
Author(s):  
Tuuli Sedman ◽  
Vallo Volke ◽  
Keiu Heinla ◽  
Eero Vasar
Keyword(s):  
Healthy Volunteers ◽  
Ambulatory Setting ◽  
Controlled Study ◽  
Acute Administration ◽  
Open Label ◽  
Glucose Levels ◽  
Adrenal Axis ◽  
Blood Glucose Levels ◽  
Glucagon Like Peptide 1 ◽  
Pituitary Adrenal Axis

AbstractGlucagon-like peptide 1 receptor agonists (GLP-1 RAs) are antidiabetic drugs with effects beyond antihyperglycemic action. The aim of the study was to examine whether a single dose of exenatide could be used as a stimulation test for the pituitary-adrenal axis. We carried out a single-group, open-label pilot clinical trial in an ambulatory setting. Ten healthy volunteers of both sexes with body weight>65 kg and age between 18–50 years were recruited. After fasting for 12 hours the subjects received 10 μg of exenatide solution subcutaneously. Blood samples were taken before the administration of exenatide and up to 150 minutes thereafter. The primary outcome was the maximal level of cortisol after the administration of exenatide. Single administration of exenatide 10 μg resulted in a modest increase in ACTH and cortisol levels, as compared to untreated values, and a decrease in blood glucose levels. Remarkably, a robust suppression of both renin and aldosterone levels occurred. We showed that acute administration of exenatide in a full therapeutic dose modestly stimulates the hypothalamic-pituitary-adrenal axis but inhibits the renin-aldosterone system. Further research is warranted to confirm this finding in the placebo-controlled study.

Prediabetes, undiagnosed diabetes and diabetes risk in Italy in 2017–2018: results from the first National screening campaign in community pharmacies

2021 ◽  
Author(s):  
P Brunetti ◽  
L Baldessin ◽  
S Pagliacci
Keyword(s):  
High Risk ◽  
Diabetes Risk ◽  
World Health ◽  
Undiagnosed Diabetes ◽  
Community Pharmacies ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Health Organization ◽  
Very High

Abstract Background Effective policies for diabetes prevention remain urgent. We conducted a mass screening campaign in Italy to identify subjects potentially having undiagnosed diabetes, prediabetes or at diabetes risk. Methods This cohort study was conducted in community pharmacies joining the unitary National federation of pharmacy holders (Federfarma) and participating in the 7-day screening campaign ‘DiaDay’ in 2017–2018. Capillary blood glucose levels and the risk of developing diabetes in 10 years (through the Finnish Diabetes Risk Score) were assessed. Results 145 651 volunteers aged ≥20 years without known diabetes were screened at 5671 community pharmacies in 2017 and 116 097 at 5112 in 2018. Overall, 3.6% had glucose values suggestive of undiagnosed diabetes; under fasting conditions (N = 94 076), 39.9% and 16.4% had values suggestive of prediabetes by the American Diabetes Association and the World Health Organization criteria, respectively. Of those without diabetes (N = 252 440), 19.2% had scores compatible with a high risk (1:3) and 2.7% with a very high risk (1:2) of developing the disease; in the prediabetes group, the risk rose with higher impaired fasting glucose values. Conclusions DiaDay, the first National screening campaign, highlights the need to screen the population and the key role of the pharmacist both in screening activities and education promotion.

The Role of Biomaterials in Insulin Delivery Systems

1980 ◽  
Vol 3 (5) ◽  
pp. 299-304 ◽  
Author(s):  
S.D. Bruck
Keyword(s):  
Blood Glucose ◽  
Glucose Sensor ◽  
Insulin Delivery ◽  
The United States ◽  
Delivery Systems ◽  
Open Loop ◽  
Health Concern ◽  
Glucose Levels ◽  
Blood Glucose Levels

The control of blood glucose levels in diabetes involving devices are critically reviewed, and the role of blood-contacting biomaterial components analyzed. These include mechanical insulin-delivery systems of the closed-loop type that require an electronic glucose sensor and feedback, and open-loop systems that deliver insulin without a sensor and feedback. Whole pancreatic and islet transplantations, islet encapsulation, and the potential role of polymeric sustained drug delivery systems are discussed. The medical and social impacts of diabetes mellitus are of prime public health concern and of even greater magnitude than those of heart disease in the United States. While future advances in device design, miniaturization, and biometrials technology will significantly add to the arsenal of therapeutic alternatives, devices capable of controlling blood glucose levels ought to be viewed as mere interim phases rather than as final goals of the problem.

Liver glycogen content decreases during meals in rats

1982 ◽  
Vol 243 (3) ◽  
pp. R450-R453
Author(s):  
W. Langhans ◽  
N. Geary ◽  
E. Scharrer
Keyword(s):  
Blood Glucose ◽  
Glycogen Content ◽  
Liver Glycogen ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Liver Glycogen Content ◽  
Ad Libitum ◽  
Portal Veins ◽  
Hepatic Portal

The effects of feeding on liver glycogen content and blood glucose in the hepatic and hepatic portal veins were investigated in rats. Liver glycogen content decreased about 25% during meals both in rats refed after 12 h food deprivation (23 +/- 1 to 17 +/- 1 mg glycogen/g liver) and in ad libitum-fed rats taking fully spontaneous meals (44 +/- 2 to 32 +/- 2 mg/g). Liver glycogen began to increase within 30 min after meals in ad libitum-fed rats. Hepatic vein blood glucose levels at meal onset (118 +/- 4 mg/dl in the food-deprived rats, 127 +/- 4 in ad libitum-fed rats) and at meal end (155 +/- 3 and 166 +/- 5 mg/dl, respectively) were similar in the two groups. Portal vein blood glucose increased during meals in the previously food-deprived rats (83 +/- 4 to 116 +/- 6 mg/dl) but not in the ad libitum-fed rats (127 +/- 5 to 132 +/- 3 mg/dl). Mechanisms that may elicit prandial glycogenolysis and the possible role of this effect in the production of meal ending satiety are discussed.

scholarly journals Depletion of Cholesteryl Esters Causes Meibomian Gland Dysfunction-Like Symptoms in a Soat1-Null Mouse Model

2021 ◽  
Vol 22 (4) ◽  
pp. 1583
Author(s):  
Igor A. Butovich ◽  
Amber Wilkerson ◽  
Seher Yuksel
Keyword(s):  
Mouse Model ◽  
High Resolution Mass Spectrometry ◽  
Meibomian Gland ◽  
Lipid Homeostasis ◽  
Null Mouse ◽  
Complete Suppression ◽  
Cholesteryl Esters ◽  
Wild Type ◽  
Massive Accumulation

Previous studies on ablation of several key genes of meibogenesis related to fatty acid elongation, omega oxidation, and esterification into wax esters have demonstrated that inactivation of any of them led to predicted changes in the meibum lipid profiles and caused severe abnormalities in the ocular surface and Meibomian gland (MG) physiology and morphology. In this study, we evaluated the effects of Soat1 ablation that were expected to cause depletion of the second largest class of Meibomian lipids (ML)—cholesteryl esters (CE)—in a mouse model. ML of the Soat1-null mice were examined using liquid chromatography high-resolution mass spectrometry and compared with those of Soat1+/− and wild-type mice. Complete suppression of CE biosynthesis and simultaneous accumulation of free cholesterol (Chl) were observed in Soat1-null mice, while Soat1+/− mutants had normal Chl and CE profiles. The total arrest of the CE biosynthesis in response to Soat1 ablation transformed Chl into the dominant lipid in meibum accounting for at least 30% of all ML. The Soat1-null mice had clear manifestations of dry eye and MG dysfunction. Enrichment of meibum with Chl and depletion of CE caused plugging of MG orifices, increased meibum rigidity and melting temperature, and led to a massive accumulation of lipid deposits around the eyes of Soat1-null mice. These findings illustrate the role of Soat1/SOAT1 in the lipid homeostasis and pathophysiology of MG.

Capsaicin-sensitive nerves are required for glucostasis but not for catecholamine output during hypoglycemia in rats

1990 ◽  
Vol 258 (1) ◽  
pp. E212-E219 ◽  
Author(s):  
X. F. Zhou ◽  
K. H. Jhamandas ◽  
B. G. Livett
Keyword(s):  
Blood Glucose ◽  
Somatostatin Analogue ◽  
Plasma Epinephrine ◽  
Conscious Rat ◽  
Glucose Response ◽  
Conscious Rats ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sensory Fibers

We have studied the glucose response and catecholamine (CA) response to insulin in the conscious rat to evaluate the role of sensory fibers in these responses in animals pretreated with capsaicin as neonates. In contrast to previous results obtained in anesthetized rats (Z. Khalil, B.G. Livett, and P.D. Marley. J. Physiol. Lond. 370: 201-215, 1986; Z. Khalil, B.G. Livett, and P.D. Marley. J. Physiol. Lond. 391: 511-526, 1987.), in conscious rats, insulin (1 IU/kg iv) produced only a mild hypoglycemia, which quickly returned to resting levels and caused no significant changes in plasma epinephrine levels. Somatostatin and SMS-(201-995), a somatostatin analogue, both potentiated and prolonged the insulin-induced hypoglycemia, resulting in an increase in circulating CA levels that was suppressed by hexamethonium and atropine. In capsaicin-pretreated rats the blood glucose levels at 90 min after insulin were significantly lower than those in vehicle-pretreated rats both in the presence (1 IU/kg insulin, 48 +/- 6 vs. 92 +/- 6 mg/100 ml, P less than 0.01) and absence (10 IU/kg insulin, 38 +/- 4 vs. 51 +/- 2 mg/100 ml, P less than 0.01) of SMS-(201-995). The CA levels in capsaicin-pretreated rats at 90 min after insulin were higher than in vehicle-pretreated rats (epinephrine levels: 27 +/- 4 vs. 10 +/- 1 pmol/ml in 1 IU/kg insulin, P less than 0.01; 64 +/- 14 vs. 25 +/- 5 pmol/ml in 10 IU/kg insulin, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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