Effects of streptozotocin-induced diabetes on feeding stimulated by centrally administered opioid agonists

Gosnell, Blake A.; Grace, Martha K.; Billington, Charles J.; Levine, Allen S.

doi:10.1016/0024-3205(89)90432-3

Cited by 15 publications

(3 citation statements)

References 27 publications

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“…Many studies have indicated that diabetes or hyperglycemia alters the sensitivity of animals to various agents [15,16]. It has also been demonstrated that diabetic animals are more sensitive than the normal controls to the hyperphagic effect of agonists specific to opioid m-receptors [17]. In the present study, we provided supportive evidence for the plasma glucose-lowering effect and increase in gene expression.…”

Section: Discussionsupporting

confidence: 82%

Increase of Opioid μ-Receptor Gene Expression in Streptozotocin-Induced Diabetic Rats

Cheng¹,

Liu²,

Chi³

et al. 2001

Horm Metab Res

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Opioids play an important role in the regulation of glucose homeostasis. In the previous report, we showed that activation of opioid mu-receptors produced a plasma glucose lowering effect in diabetic rats lacking insulin. In the present study, we found that the response of opioid mu-receptor is more sensitive in streptozotocin-induced diabetic rats (STZ-diabetic rats) than in normal rats. Intravenous injection of loperamide, an agonist of opioid mu-receptors, induced a dose-dependent decrease of plasma glucose from 3 microg/kg to 60 microg/kg in fasting STZ-diabetic rats. However, loperamide decreased the plasma glucose of normal fasting rats at the doses of 0.3 mg/kg to 1.5 mg/kg, which were much higher than those needed to produce the same effect in diabetic rats. The plasma glucose-lowering action of loperamide at the dose effective in normal rats disappeared in opioid mu-receptor knockout mice, while the plasma glucose-lowering response to loperamide was still observed in wild-type mice. This opens the possibility of mediation through opioid mu-receptor in the plasma glucose-lowering action of loperamide. Moreover, the mRNA level of opioid mu-receptor in the liver markedly increased in STZ-diabetic rats compared to normal rats. Normalization of plasma glucose concentrations in STZ-diabetic rats with exogenous insulin or phlorizin reversed mRNA and protein levels of opioid mu-receptor in the liver after 4 days of treatment. This shows that correction of hyperglycemia in STZ-diabetic rats may reverse the higher gene expression of opioid mu-receptor. These results suggest that hyperglycemia is responsible for increase of opioid mu-receptor in STZ-diabetic rats.

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Section: Discussionsupporting

confidence: 82%

Increase of Opioid μ-Receptor Gene Expression in Streptozotocin-Induced Diabetic Rats

Cheng¹,

Liu²,

Chi³

et al. 2001

Horm Metab Res

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“…For instance, it has been well known that diabetes or hyperglycemia influences the sensitivity of experimental animals to various medicines (24,25). Furthermore, it has been reported that mice and rats with streptozotocin-induced diabetes and spontaneous diabetic mice are significantly less sensitive than nondiabetic mice to the antinociceptive effect of morphine (26). Moreover, it has been well established that anxiety and depression are common in patients with diabetes (27,28), and it has been shown that anxiogenic activity, itself, induces a significant increase in serum level of glucose (29).…”

Section: Discussionmentioning

confidence: 98%

Opium and Heroin Alter Biochemical Parameters of Human's Serum

Divsalar

Haghpanah

Afarinesh

et al. 2010

The American Journal of Drug and Alcohol Abuse

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“…Many studies have indicated that diabetes or hyperglycaemia alter the sensitivity of animals to various agents [61, 62]. It has also been demonstrated that diabetic animals are more sensitive than normal controls to the hyperphagic effect of agonists specific to MOR [63]. However, diabetic animals are less sensitive than normal controls to anti-nociceptive action mediated by supraspinal MOR [64, 65].…”

Section: Peripheral Mor Activation Participates In the Plasma Glucmentioning

confidence: 99%

Mediation of Endogenous β‐Endorphin in the Plasma Glucose‐Lowering Action of Herbal Products Observed in Type 1‐Like Diabetic Rats

Liu

Cheng

2010

Evidence-Based Complementary and Alternative Medicine

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Recently, there have been advances in the development of new substances effective in managing diabetic disorders. Opioid receptors couple multiple systems to result in various biological effects, although opioids are best known for analgesia. In the present review, we used our recent data to describe the advance in plasma glucose-lowering action of herbal products, especially the mediation of β-endorphin in glucose homeostasis of insulin-deficient diabetes. In type 1-like streptozotocin-induced diabetic rats, we identified many products purified from herbs that show a dose-dependent plasma glucose-lowering action. Increase in β-endorphin secretion from the adrenal gland may activate peripheral opioid μ-receptors (MOR) to enhance the expression of muscle glucose transporters and/or to reduce hepatic gluconeogenesis at the gene level, thereby leading to improved glucose utilization in peripheral tissues for amelioration of severe hyperglycemia. It has also been observed that stimulation of α 1-adrenoceptors (α 1-ARs) in the adrenal gland by some herbal products is responsible for the increase in β-endorphin secretion via a phospholipase C-protein kinase dependent pathway. However, an increase in β-endorphin secretion from the adrenal gland by herbal products can function via another receptor. New insights into the mediation of endogenous β-endorphin activation of peripheral MOR by herbal products for regulation of glucose homeostasis without the presence of insulin have been established. Therefore, an increase in β-endorphin secretion and/or direct stimulation of peripheral MOR via an insulin-independent action might serve as the potential target for development of a therapeutic agent or promising adjuvant in intensive plasma glucose control.

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Effects of streptozotocin-induced diabetes on feeding stimulated by centrally administered opioid agonists

Cited by 15 publications

References 27 publications

Increase of Opioid μ-Receptor Gene Expression in Streptozotocin-Induced Diabetic Rats

Increase of Opioid μ-Receptor Gene Expression in Streptozotocin-Induced Diabetic Rats

Opium and Heroin Alter Biochemical Parameters of Human's Serum

Mediation of Endogenous β‐Endorphin in the Plasma Glucose‐Lowering Action of Herbal Products Observed in Type 1‐Like Diabetic Rats

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