scholarly journals Long-Term Effects of Central Leptin and Resistin on Body Weight, Insulin Resistance, and β-Cell Function and Mass by the Modulation of Hypothalamic Leptin and Insulin Signaling

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 445-454 ◽  
Author(s):  
Sunmin Park ◽  
Sang Mee Hong ◽  
So Ra Sung ◽  
Hye Kyung Jung
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Insulin Signaling ◽  
Cell Function ◽  
Cell Mass ◽  
Diabetic Rats ◽  
Β Cell ◽  
Serum Leptin ◽  
Β Cell Function

To determine the long-term effect of central leptin and resistin on energy homeostasis, peripheral insulin resistance, and β-cell function and mass, intracerebroventricular (ICV) infusion of leptin (3 ng/h), resistin (80 ng/h), leptin plus resistin, and cerebrospinal fluid (control) was conducted by means of an osmotic pump for 4 wk on normal rats and 90% pancreatectomized diabetic rats fed 40% fat-energy diets. Overall, the effects were greater in diabetic rats than normal rats. Leptin infusion, causing a significant reduction in food intake, decreased body weight and epididymal fat. However, resistin and leptin plus resistin reduced epididymal fat with decreased serum leptin levels in comparison with the control. Unlike serum leptin, only resistin infusion lowered serum resistin levels. Central leptin increased glucose infusion rates during euglycemic hyperinsulinemic clamp and suppressed hepatic glucose production in the hyperinsulinemic state in comparison with the control. However, central leptin did not affect glucose-stimulated insulin secretion and β-cell mass. Central resistin infusion also increased peripheral insulin sensitivity, but not as much as leptin. Unlike leptin, resistin significantly increased first-phase insulin secretion during hyperglycemic clamp and β-cell mass by augmenting β-cell proliferation. These metabolic changes were associated with hypothalamic leptin and insulin signaling. ICV infusion of leptin potentiated signal transducer and activator of transcription 3 phosphorylation and attenuated AMP kinase in the hypothalamus, but resistin had less potent effects than leptin. Leptin enhanced insulin signaling by potentiating IRS2→Akt pathways, whereas resistin activated Akt without augmenting insulin receptor substrate 2 phosphorylation. In conclusion, long-term ICV infusion of leptin and resistin independently improved energy and glucose homeostasis by modulating in different ways hypothalamic leptin and insulin signaling.

Islet Cell Mass and the Longevity of Islet Grafts in Diabetic Rats

1993 ◽  
Vol 2 (2) ◽  
pp. 119-122 ◽  
Author(s):  
Gillian M. Beattie ◽  
Alberto Hayek
Keyword(s):  
Islet Cell ◽  
Cell Function ◽  
Cell Mass ◽  
Close Correlation ◽  
Diabetic Rats ◽  
Islet Graft ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucose Tolerance Tests ◽  
Islet Transplants

In an attempt to demonstrate that a limited β-cell mass is able to maintain normoglycemia in streptozocin-diabetic rats, two groups of inbred rats received transplants of 500 or 1000 neonatal islets (corresponding to 10 and 20% of total islet cell mass, respectively) into the spleen. A close correlation was found between the functional longevity of the islet graft, and the total β-cell mass transplanted into the diabetic animals. Although euglycemia was maintained for 4-12 mo, the islet transplants were insufficient to produce glucose tolerance tests equal to those observed in normal rats. Relapse of diabetes correlated with histological findings of distorted islet architecture containing vacuolated β-cells in the grafts. This condition was not reversed after a month of normoglycemia. Spontaneous recovery of β-cell function in native islets was documented in 50% of the diabetic rats with prolonged normoglycemia following islet transplantation. This report shows that transplantation of as few as 500 neonatal islets, the equivalent of 10% of total islet cell mass, is sufficient to maintain normoglycemia in diabetic rats, albeit temporarily. A close correlation was found between the transplanted islet cell mass and the functional longevity of the islet graft.

Exercise improves glucose homeostasis that has been impaired by a high-fat diet by potentiating pancreatic β-cell function and mass through IRS2 in diabetic rats

2007 ◽  
Vol 103 (5) ◽  
pp. 1764-1771 ◽  
Author(s):  
Sunmin Park ◽  
Sang Mee Hong ◽  
Ji Eun Lee ◽  
So Ra Sung
Keyword(s):  
Cell Proliferation ◽  
High Fat Diet ◽  
Cell Function ◽  
Cell Mass ◽  
Diabetic Rats ◽  
Pancreatic Β Cell ◽  
High Fat ◽  
Β Cell ◽  
Igf I ◽  
Β Cell Function

In this study, we investigated the effects of a high-fat diet and exercise on pancreatic β-cell function and mass and its molecular mechanism in 90% pancreatectomized male rats. The pancreatectomized diabetic rats were given control diets (20% energy) or a high-fat (HF) diet (45% energy) for 12 wk. Half of each group was given regular exercise on an uphill treadmill at 20 m/min for 30 min 5 days/wk. HF diet lowered first-phase insulin secretion with glucose loading, whereas exercise training reversed this decrease. However, second-phase insulin secretion did not differ among the groups. Exercise increased pancreatic β-cell mass. This resulted from stimulated β-cell proliferation and reduced apoptosis, which is associated with potentiated insulin or IGF-I signaling through insulin receptor substrate-2 (IRS2) induction. Although the HF diet resulted in decreased proliferation and accelerated apoptosis by weakened insulin and IGF-I signaling from reduction of IRS2 protein, β-cell mass was maintained in HF rats just as much as in control rats via increased individual β-cell size and neogenesis from precursor cells. Consistent with the results of β-cell proliferation, pancreas duodenal homeobox-1 expression increased in the islets of rats in the exercise groups, and it was reduced the most in rats fed the HF diet. In conclusion, exercise combined with a moderate fat diet is a good way to maximize β-cell function and mass through IRS2 induction to alleviate the diabetic condition. This study suggests that dietary fat contents and exercise modulate β-cell function and mass to overcome insulin resistance in two different pathways.

Effect of Marantodes pumilum Blume (Kuntze) var.alata on β-cell function and insulin signaling in ovariectomised diabetic rats

Phytomedicine ◽  
2019 ◽  
Vol 65 ◽  
pp. 153101 ◽  
Author(s):  
M. Dharmani ◽  
K. Kamarulzaman ◽  
N. Giribabu ◽  
K.W. Choy ◽  
M.Z. Zuhaida ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Cell Function ◽  
Diabetic Rats ◽  
Β Cell ◽  
Β Cell Function

scholarly journals Effect of different exercise trainings on β-cell function, insulin resistance, and osteocalcin levels in overweight men

2021 ◽  
Vol 23 (3) ◽  
pp. 116-123
Author(s):  
Mehdi Rostamizadeh ◽  
Alireza Elmieh ◽  
Farhad Rahmani Nia
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Resistance Exercise ◽  
Aerobic Exercise ◽  
Cell Function ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Β Cell ◽  
Supervised Exercise ◽  
Β Cell Function

Background and aims: Many findings have shown the potential relation between osteocalcin (OCN) and regulating energy metabolism. In addition, it has been revealed that physical activity increases OCN levels. Therefore, the present study aimed to investigate the effects of different exercise trainings on β-cell function, insulin resistance, and OCN levels in overweight men. Methods: In this study, 33 overweight, young men [Body mass index (BMI): 29.32±0.75 and age range of 31.50±2.23] were randomly divided into control (n=11), aerobic exercise (n=11), and resistance exercise (n=11) groups. Participants of the exercise group were on the 8-week supervised exercise training program for three sessions per week. Weight, body fat percentage, and BMI were analyzed, and then OCN, insulin, and the homeostasis model assessment of insulin resistance (HOMA-IR) were assessed from fasting blood samples before and after the 8-week exercise program. Finally, data were analyzed by t test and analysis of covariance (ANCOVA). Results: Based on the results, BMI and body weight, insulin, glucose, and HOMA-IR reduced following the exercise (P<0.05) whereas serum OCN significantly increased in aerobic exercise (P=0.001) and resistance exercise (P=0.000) groups. There were no significant changes in β-cell function in aerobic exercise (P=0.512) and resistance exercise (P=0.16) groups. Pearson correlation analysis demonstrated that OCN levels were not correlated with HOMA-IR (P=0.743) and insulin levels (P=0.143). However, OCN was positively associated with the homeostasis model assessment of b-cell function (P=0.014) and glucose (P=0.025). Conclusion: The results of the present study confirmed that aerobic and resistance exercises cause some changes in body weight and BMI, as well as the OCN and HOMA-IR. Nonetheless, changes in OCN levels were not predictors of changes in insulin secretion from pancreatic beta cells.

Genetic Polymorphisms of β-Cell Differentiation Confer Risk of Alterations of Glucose Metabolism in Survivors of Childhood Acute Lymphoblastic Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1908-1908
Author(s):  
Pacharapan Surapolchai ◽  
Suradej Hongeng ◽  
Pat Mahachoklertwattana ◽  
Samart Pakakasama ◽  
Angkana Winaichatsak ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Lymphoblastic Leukemia ◽  
Β Cell ◽  
Childhood All ◽  
Β Cell Function

Abstract Purpose: Long-term survivors of acute lymphoblastic leukemia (ALL) seem to be at risk of insulin resistance, impaired glucose tolerance and may develop typical signs of metabolic syndrome with disturbances in lipid metabolism. The aim of the present study was to study the prevalence of alterations in glucose metabolism and the predisposing factors of these disturbances in survivors of childhood ALL. Furthermore, we intended to identify the role of such genetic polymorphisms affecting β-cell function and glucose metabolism and possibly to develop them as markers for monitoring β-cell dysfunction following treatment for ALL in the future. Patients and methods: In 131 ALL survivors after cessation of therapy, an oral glucose tolerance test was performed to determine β-cell function/insulin sensitivity. Six single-nucleotide polymorphisms of PAX4 and TCF7L2 genes were genotyped in order to evaluate the association between these polymorphisms and β-cell function/insulin sensitivity. Results: Ten out of 131 (7.6%) survivors had impaired glucose tolerance (IGT) while 40 out of 131 (30.5%) had insulin resistance (IR) and demonstrated characteristics of metabolic syndrome (hyperinsulinemia, hypertriglyceridemia, low HDL-C). In the logistic regression analysis, the most important factor predicting IGT and IR was older current age (p= 0.010 and &lt;0.001, respectively) while the PAX4 R192H mutation (rs2233580) was significant associated only to IGT after adjusted for age (p=0.043) (adjusted OR 5.28, 95%CI 1.06–26.40). Conclusion: Our findings suggest that older age of childhood ALL survivors is the most important risk factor of IGT and IR, underlining the need to continue regular and long-term screening till adulthood. Moreover, after adjusted for age, the PAX4 R192H variant (rs2233580) seemed to be associated with IGT. If this association is confirmed, institution of lifestyle and therapeutic measures may be needed to reduce metabolic risk and diabetes.

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