scholarly journals Euglycemic Infusion of Insulin Detemir Compared With Human Insulin Appears to Increase Direct Current Brain Potential Response and Reduces Food Intake While Inducing Similar Systemic Effects

Diabetes ◽  
2010 ◽  
Vol 59 (4) ◽  
pp. 1101-1107 ◽  
Author(s):  
M. Hallschmid ◽  
K. Jauch-Chara ◽  
O. Korn ◽  
M. Molle ◽  
B. Rasch ◽  
...  
Keyword(s):  
Food Intake ◽  
Human Insulin ◽  
Direct Current ◽  
Insulin Detemir ◽  
Systemic Effects ◽  
Potential Response ◽  
Brain Potential

Evaluation of the lack of anorectic effect of intracerebroventricular insulin in rats

2010 ◽  
Vol 298 (1) ◽  
pp. R43-R50 ◽  
Author(s):  
Lene Jessen ◽  
Deborah J. Clegg ◽  
Stephan D. Bouman
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Human Insulin ◽  
Insulin Detemir ◽  
Positive Control ◽  
Published Data ◽  
Diabetic Patients ◽  
Regular Human Insulin ◽  
Anorectic Effect ◽  
Inhibit Food Intake

Insulin detemir is a novel human insulin analog that does not show the usual propensity for weight gain in diabetic patients. We speculated that this beneficial effect could be due to insulin detemir exerting stronger anorectic effects within the brain than other insulins. To study the central effects of regular human insulin and insulin detemir on food intake, the present study was undertaken. We used acute intracerebroventricular insulin injections to compare food intake and body weight in rats fed ad libitum. Contrary to previously published data, we found that neither regular human insulin (8 or 32 mU) nor insulin detemir (1,290 pmol) reduced food intake in this model. Melanotan-II was also injected intracerebroventricularly as a positive control, and significantly reduced food intake and body weight, suggesting that our intracerebroventricular model is able to show anorectic effects. A series of experiments was therefore conducted in which different set-ups were tested to investigate which factors would be required to produce the reported anorectic effect of intracerebroventricular insulin. Although we varied rat strain, stereotactic coordinates, formulations of insulin and vehicle, dose, volume, and time of injection, the anorectic effect of intracerebroventricular insulin could not be replicated. Therefore, we suggest that acute intracerebroventricularly injected insulin does not robustly inhibit food intake in rats. Based on our results, the acute intracerebroventricular injection procedure may not be a preferred method for studying the central anorectic effects of insulin in rats. Instead, administrations over time or locally in hypothalamic nuclei might be recommended.

Effects of normal human insulin, insulin aspart, and insulin detemir on the lifespan of Caenorhabditis elegans

2008 ◽  
Vol 3 (S 1) ◽  
Author(s):  
Y Ibrahim ◽  
A Schlotterer ◽  
G Kukudov ◽  
P Humpert ◽  
G Rudofsky ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Human Insulin ◽  
Insulin Aspart ◽  
Insulin Detemir ◽  
Normal Human

Capsaicin-sensitive fibers are required for the anorexic action of systemic but not central bombesin

1999 ◽  
Vol 276 (6) ◽  
pp. R1617-R1622 ◽  
Author(s):  
David Michaud ◽  
Hymie Anisman ◽  
Zul Merali
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Neural Circuits ◽  
Body Weight Gain ◽  
Systemic Effects ◽  
Neuronal System ◽  
Afferent Neurons ◽  
The Brain

Bombesin (BN) suppresses food intake in rats whether given centrally or systemically. Although the brain BN-sensitive receptors are known to be essential for the anorexic effect of systemic BN, the mode of communication between the gut and the brain remains unclear. This study assessed whether the anorexic effect of systemic BN is mediated humorally or via neural circuits. Afferent neurons were lesioned using capsaicin (50 mg/kg sc) on postnatal day 2, and responses to BN were assessed during adulthood. Capsaicin treatment decreased body weight gain significantly from postnatal age 4–7 wk. Peripheral BN (4–16 μg/kg ip) dose dependently suppressed food intake in control animals. However, this effect was completely blocked in capsaicin-treated rats. In contrast to systemic effects, feeding-suppressant effects of centrally administered BN (0.01–0.5 μg icv) were not affected by capsaicin treatment. This research suggests that peripheral BN communicates with the brain via a neuronal system(s) whose afferent arm is constituted of capsaicin-sensitive C and/or Aδ-fibers, whereas the efferent arm of this satiety- and/or anorexia-mediating circuitry is capsaicin resistant.

Evaluation of Cell Proliferation in Rat Mammary Glands Is Not Predictive of the Carcinogenic Potential of Insulin In Vivo

2020 ◽  
Vol 39 (6) ◽  
pp. 560-576
Author(s):  
Vivi Flou Hjorth Jensen ◽  
Peter R. Brinck ◽  
Jette Nowak ◽  
Inger Thorup ◽  
Ingrid Sjögren ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Human Insulin ◽  
Safety Assessment ◽  
Insulin Detemir ◽  
Mammary Glands ◽  
Positive Control ◽  
Mitogenic Effect ◽  
Carcinogenic Potential ◽  
Histopathologic Evaluation

For nonclinical safety-assessment of insulin analogues in vivo, mitogenic effects are compared to that of human insulin. Besides histopathologic evaluation, this usually includes assessment of cell proliferation (CP) in mammary glands. Insulin analogue X10 is recommended as positive control, due to its known carcinogenic effect in rat mammary glands. Here, we discuss the mitogenic effect of insulin in vivo and use of X10 as positive control. We present results from 4 nonclinical rat studies evaluating effects of repeated dosing with insulin detemir (≤26 weeks) or degludec (52 weeks) in mammary glands. Studies included human insulin-dosed groups as comparators, CP, and histopathologic evaluation. One study included an X10-dosed group (26 weeks), another ≤3 weeks of dosing with X10 or human insulin evaluating effects of these comparators. Neither human insulin, insulin detemir, degludec, nor X10 induced mammary tumors or increased CP in the studies. The CP marker proliferating cell nuclear antigen varied within/between studies and was not correlated with the remaining markers or CP fluctuations during estrous cycle, whereas the other CP markers, Ki-67 and 5-bromo-2′-deoxyuridine (BrdU), correlated with estrous cycle changes and each other. In conclusion, we propose that the mitogenic effect of insulin in rat mammary glands is weak in vivo. Cell proliferation evaluation in nonclinical safety assessment studies is not predictive of the carcinogenic potential of insulin, thus, the value of including this end point is debatable. Moreover, X10 is not recommended as positive control, due to lack of proliferative effects. Typical CP markers vary greatly in quality, BrdU seemingly most reliable.

Insulin detemir causes increased symptom awareness during hypoglycaemia compared to human insulin

2009 ◽  
Vol 11 (11) ◽  
pp. 1017-1026 ◽  
Author(s):  
O. Tschritter ◽  
S. A. Schäfer ◽  
J. Klett ◽  
A. Pfäfflin ◽  
H.-U. Häring ◽  
...  
Keyword(s):  
Human Insulin ◽  
Insulin Detemir ◽  
Symptom Awareness

scholarly journals ORLISTAT IN COMBINATION THERAPY OF OBESITY AND TYPE 2 DIABETES

2017 ◽  
pp. 68-74 ◽  
Author(s):  
A. M. Mkrtumyan ◽  
E. V. Biryukova
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Clinical Trials ◽  
Food Intake ◽  
Combination Therapy ◽  
Systemic Effects ◽  
The Past ◽  
Prevention And Treatment ◽  
Treatment Of Obesity

Over the past years, the focus has been growing on the prevention and treatment of obesity. Obesity has long been considered not just as excess body fat but as a chronic relapsing disease, the result of energy disbalance, which develops with an increase in food intake and reduced energy expenditure and is closely associated with a number of serious complications. Orlistat (Xenical), a peripherally acting drug without systemic effects [11, 24, 27], has been widely used in pharmacological treatment of obesity. Xenical is the most well-studied medication for weight loss. More than 30,000 patients with obesity were involved in clinical trials, of which over 2,500 patients had type 2 diabetes. Till today, the drug remains a breakthrough in the treatment of overweight/obesity.

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