Hypoglycemic effects of a β-agonist, Ro 16-8714, in streptozotocin-diabetic rats: Decreased hepatic glucose production and increased glucose utilization in oxidative muscles

Ferré, Pilar; Pénicaud, Luc; Hitier, Y; Meier, M.; Girard, Jean

doi:10.1016/0026-0495(92)90149-5

Cited by 9 publications

(7 citation statements)

References 17 publications

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“…Some studies have reported that β 3 ‐adrenergic agonists may be able to regulate glucose homeostasis in cases of hyperglycaemia and diabetes mellitus, both in rodents with genetically‐[3, 13, 33] chemically‐induced[9] diabetes mellitus. However, the mechanisms remain still unclear.…”

Section: Discussionmentioning

confidence: 99%

A b₃‐adrenergic agonist increases muscle GLUT1/GLUT4 ratio, and regulates liver glucose utilization in diabetic rats*

Milagro¹,

Gómez-Ambrosi²,

Forga³

et al. 1999

Diabetes Obesity Metabolism

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Trecadrine reduces glucose output from the liver, thus thus contributing to the reduction of plasma glucose levels to achieve the values of control rats. Furthermore, Trecadrine administration stimulates glucose uptake in skeletal muscle, especially in those muscles with predominant glycolytic fast-twitched fibres, apparently by a direct non-insulin-dependent mechanism, involving a relative increase in the content of GLUT1 in the plasma membrane as compared with GLUT4. In conclusion, Trecadrine shows a potent hypoglycaemic effect in the alloxan-induced model of diabetes in rats by decreasing hepatic glucose output and improving muscle glucose uptake.

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Section: Discussionmentioning

confidence: 99%

A b₃‐adrenergic agonist increases muscle GLUT1/GLUT4 ratio, and regulates liver glucose utilization in diabetic rats*

Milagro¹,

Gómez-Ambrosi²,

Forga³

et al. 1999

Diabetes Obesity Metabolism

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show abstract

“…In addition to the antidiabetic activity that occurred secondary to weight loss, BRL 26830, BRL 35135, and Ro 16-8714 were also reported to have antidiabetic activity independent of their antiobesity activity. These studies were conducted under two conditions: a) compounds were given by single administration (73,78) or b) compounds were given chronically at doses that did not cause weight loss or reduced weight gain (10,14,15,17,29,78).…”

Section: Antidiabetesmentioning

confidence: 99%

“…Similar treatments of obesediabetic animals either had no effect (73) or exacerbated the diabetic conditions by increasing glucose intolerance (15,73,78) or increasing blood glucose concentrations (10.78,89,100). In contrast, chronic administration of these compounds improved insulin sensitivity of obesediabetic animals (10,15,17,78) which resulted in an improvement of glucose tolerance (73,78) and a decrease in glycemia and glycosuria (14,15,29,78).…”

Section: Antidiabetesmentioning

confidence: 99%

“…The target tissue(s) responsible for the antidiabetic action of these drugs have not been defined. Glucose utilization was increased in oxidative muscles by BRL 26830 (18) and Ro 16-8714 (29). It was suggested that brown adipose tissue is unlikely to be the target tissue because of its low overall rate to whole body glucose homeostasis (29) and glucose is not a major substrate in this tissue (49).…”

Section: Antidiabetesmentioning

confidence: 99%

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Antiobesity and Antidiabetic β‐agonists: Lessons Learned and Questions to be Answered

Yen

1994

Obesity Research

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In several species of obese animals, a group of phenethanolamine beta-agonists stimulates lipolysis and thermogenesis, resulting in the loss of body fat and weight. Brown adipose tissue is considered to be the major target tissue for the antiobesity activity of these compounds. Independent of this antiobesity activity, some of these compounds are also antidiabetic and increase muscle mass. Based on the pharmacological profile of these compounds, a beta3-receptor was proposed and characterized in mouse, rat, and humans. The beta3-receptor in brown adipose tissue has been suggested to mediate the antiobesity activity of these beta-agonists. Whether this receptor is responsible for the antidiabetic activity and whether there is a linkage between the antiobesity/antidiabetic activity and the nutrient partitioning activity is not clear. Clinical trials with these mixed beta-agonists showed marginal antiobesity effects when caloric intake of subjects was restricted. Insulin sensitivity was also improved in some of the trials designed to test the antidiabetic activity of these compounds. Side effects included tachycardia and tremor. To eliminate these side effects, a second generation of compounds was selected for its agonist activity on rat beta3-receptors. Clinical trials with these compounds have shown little increase of energy expenditure even at high doses. Successful development of an antiobesity and antidiabetic drug from this class of compounds will require the elucidation of the physiological role of the human beta3-receptor and the regulatory mechanism between fuel efficiency and feeding behavior.

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“…Some studies indicate that glucose utilization was increased by BRL 26830 (56) and Ro 16-8714 (7) in brown adipose tissue but not in muscles. Other studies using the same compounds found glucose utilization in oxidative muscles did increase (14,25). Resolving which tissue is responsible for the antidiabetic action of these compounds would facilitate the understanding of the mechanism.…”

Section: Pi-and P-pharmacological Activities In Animals and In Hu-mentioning

confidence: 99%

β‐Agonists as Antiobesity, Antidiabetic and Nutrient Partitioning Agents

Yen

1995

Obesity Research

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YEN,TERENCE T. P-agonists as antiobesity, antidiabetic and nutrient partitioning agents. Obes Res. 1995;3(SupplIn the past decade, the antiobesity, antidiabetic andnutrient partitioning activities of P-agonists have been extensively studied. Thedata generatedfromthesecompounds inexperimentalandfarmanimals haveconvincingly provedthat body fat content andbodyweightcan bemoditiedto somedegreeby a metabolic agent without decreasing food consumption. Marginal antiobesity and antidiabetic activities in humans have been demonstratedwith afew mixed P-agonists under certain conditions, but their utility is limited by side effects. The concept of a P,-receptor rose from the study of these compounds and has beenverified by the cloning and expression of this receptor from several species. Rat p,-selective agonistshaveso far shownno antiobesityefficacyinhumans. The resolution of several issues is critical for the discovery and development of efficacious antiobesity and antidiabetic agents with minimum side effects. Ultimately, the further investigationof these P-agonists and P-receptors shouldlead to a better understanding of the relationship between energy metabolism and feeding behavior.4):5318-5368.

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Hypoglycemic effects of a β-agonist, Ro 16-8714, in streptozotocin-diabetic rats: Decreased hepatic glucose production and increased glucose utilization in oxidative muscles

Cited by 9 publications

References 17 publications

A b₃‐adrenergic agonist increases muscle GLUT1/GLUT4 ratio, and regulates liver glucose utilization in diabetic rats*

A b₃‐adrenergic agonist increases muscle GLUT1/GLUT4 ratio, and regulates liver glucose utilization in diabetic rats*

Antiobesity and Antidiabetic β‐agonists: Lessons Learned and Questions to be Answered

β‐Agonists as Antiobesity, Antidiabetic and Nutrient Partitioning Agents

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Hypoglycemic effects of a β-agonist, Ro 16-8714, in streptozotocin-diabetic rats: Decreased hepatic glucose production and increased glucose utilization in oxidative muscles

Cited by 9 publications

References 17 publications

A b3‐adrenergic agonist increases muscle GLUT1/GLUT4 ratio, and regulates liver glucose utilization in diabetic rats*

A b3‐adrenergic agonist increases muscle GLUT1/GLUT4 ratio, and regulates liver glucose utilization in diabetic rats*

Antiobesity and Antidiabetic β‐agonists: Lessons Learned and Questions to be Answered

β‐Agonists as Antiobesity, Antidiabetic and Nutrient Partitioning Agents

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Product

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A b₃‐adrenergic agonist increases muscle GLUT1/GLUT4 ratio, and regulates liver glucose utilization in diabetic rats*

A b₃‐adrenergic agonist increases muscle GLUT1/GLUT4 ratio, and regulates liver glucose utilization in diabetic rats*