Endocannabinoid hydrolase and cannabinoid receptor 1 are involved in the regulation of hypothalamus-pituitary-adrenal axis in type 2 diabetes

Individuals born with a low birth weight (LBW) have an increased prevalence of type 2 diabetes, but the mechanisms responsible for this association are unknown. Given the important role of insulin resistance in the pathogenesis of type 2 diabetes, we examined insulin sensitivity in a rat model of LBW due to intrauterine fetal stress. During the last 7 days of gestation, rat dams were treated with dexamethasone and insulin sensitivity was assessed in the LBW offspring by a hyperinsulinemic euglycemic clamp. The LBW group had liver-specific insulin resistance associated with increased levels of PEPCK expression. These changes were associated with pituitary hyperplasia of the ACTH-secreting cells, increased morning plasma ACTH concentrations, elevated corticosterone secretion during restraint stress, and an ∼70% increase in 24-h urine corticosterone excretion. These data support the hypothesis that prenatal stress can result in chronic hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in increased plasma corticosterone concentrations, upregulation of hepatic gluconeogenesis, and hepatic insulin resistance.

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Is the hypothalamic–pituitary–adrenal axis disrupted in type 2 diabetes mellitus?

Endocrine ◽

10.1007/s12020-016-1108-1 ◽

2016 ◽

Vol 54 (2) ◽

pp. 273-275 ◽

Cited By ~ 5

Author(s):

Hershel Raff ◽

Steven B. Magill

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Hypothalamic Pituitary Adrenal Axis ◽

Hypothalamic Pituitary Adrenal ◽

Adrenal Axis ◽

Pituitary Adrenal Axis

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The Stress Axis in Obesity and Diabetes Mellitus: An Update

Endocrines ◽

10.3390/endocrines2030031 ◽

2021 ◽

Vol 2 (3) ◽

pp. 334-347

Author(s):

Laura Gianotti ◽

Sara Belcastro ◽

Salvatore D’Agnano ◽

Francesco Tassone

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Chronic Stress ◽

Hypothalamic Pituitary Adrenal ◽

Adrenal Axis ◽

Acute And Chronic Stress ◽

Pituitary Adrenal Axis

The hypothalamic–pituitary–adrenal axis is a tightly regulated system that represents one of the body’s mechanisms for responding to acute and chronic stress. Prolonged stress and/or inadequate regulation of the stress system can lead to a condition of chronic hypercortisolism or, in some cases, a blunted cortisol response to stress, contributing to insulin resistance, increased adiposity and type 2 diabetes mellitus. Moreover, acute and chronic stress can exacerbate or worsen metabolic conditions by supporting an inflammatory state and a tight relationship between stress, inflammation and adipose tissue has been reported and has been a growing subject of interest in recent years. We reviewed and summarized the evidence supporting hypothalamic–pituitary–adrenal axis dysregulation as an important biological link between stress, obesity, inflammation and type 2 diabetes mellitus. Furthermore, we emphasized the possible role of infectious-related stress such as SarsCov2 infection in adrenal axis dysregulation, insulin resistance and diabetes in a bidirectional link. Understanding and better defining the links between stress and obesity or diabetes could contribute to further definition of the pathogenesis and the management of stress-related complications, in which the HPA axis dysregulation has a primary role.

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