Hypothalamo-Pituitary-Adrenal (HPA) Axis and Diabetes

Tresa Anto¹, Godwin²

¹Vice Principal, Jubilee Mission College of Nursing. Jubilee Gardens, Kachery, Thrissure-5, Kerala.

²Assistant Professor, Jubilee Mission College of Nursing, Kerala.

*Corresponding Author Email: srtresaanto@gmail.com

ABSTRACT:

Hypothalamo-Pituitary-Adrenal (HPA) Axis is critical for the integration and coordination of various bodily functions. The hypothalamus serves as the integrating center for the stimuli. The hypothalamus contains neurosecretory neurons if any system in the body need any thing , the hypothalamus senses and send a correct response.Many of the metabolic disorders have an endocrine origin and are accompanied by abnormal hormone

concentrations. In human the full programming of key endocrine functions are done with help of Hypothalamo-Pituitary-Adrenal (HPA) Axis.

KEYWORDS: Hypothalamo-Pituitary-Adrenal axis , diabetes,and stress responsiveness.

INTRODUCTION:

The endocrine system is critical for the integration and coordination of various bodily functions. The hypothalamus serves as the integrating center for the stimuli. The hypothalamus contains neurosecretory neurons which synthesize peptides and catecholamines; these are released into the circulatory system and act as hormones.

These responses are mediated in large part by the neuroendocrine and endocrine signals originating along the hypothalamo-pituitary axis. For example, if a person finds him/her self dehydrated, the hypothalamus senses the increase in osmotic strength of the extracellular fluids. In parallel, the loss of extracellular volume is sensed by the peripheral nervous system and this information is also relayed to the hypothalamus. These stimuli result in a number of different responses, including the release of ADH in the posterior pituitary which will preserve the water in kidneys and stimulate thirst. An additional hypothalamic response in this situation might be release of corticotrophin-releasing hormone (CRH) in response to stress. CRH will target the anterior pituitary to release adrenocorticotrophic hormone (ACTH) and subsequently release glucocorticoids from the adrenal gland^1.

HPA axis and diabetes:

Many of the metabolic disorders have an endocrine origin and are accompanied by abnormal hormone concentrations. In humans, low birth weight is associated with an increased risk of metabolic dysfunction in adult life. In humans, low birth weight is associated with an increased risk of metabolic dysfunction in adult life. This has led to the hypothesis that adult metabolic disease arises in utero as a result of programming of key endocrine systems during suboptimal intrauterine conditions associated with fetal growth retardation. The prenatal endocrine programming with endocrine axes involved in growth and metabolism, namely, the hypothalamic–pituitary–adrenal axis, the endocrine pancreas and the somatotrophic axis. It also considers how changes in these endocrine systems contribute to the programming of metabolism in later life^2.

stress responsiveness and diabetes:

Patients and animals with poorly controlled or uncontrolled diabetes present with hypersecretion of glucocorticoids and altered regulation of the hypothalamo-pituitary-adrenocortical (HPA) axis. In addition, stress responsiveness is also impaired in diabetes and this has important implications in the way patients with diabetes cope with many stress challenges, including the metabolic challenge of insulin-induced hypoglycemia. HPA dysregulation in diabetes appears to involve complex interactions between impaired glucocorticoid negative feedback sensitivity and factors such as hypoinsulinemia, hyperglycemia and/or hypoleptinemia, that may increase central drive of the axis^3.

Memory Impairments and diabetes:

There is an hypothalamic-pituitary-adrenocortical (HPA) axis and cognitive dysfunction in type 2 diabetes mellitus (T2DM).Among individuals with T2DM, cortisol levels were positively associated with glycosylated hemoglobin, independent of age, body mass index, hypertension, and dyslipidemia. Diabetic subjects has cognitive impairments restricted to declarative memory. HPA hyperactivity and declarative memory deficits are present in T2DM. Both alterations may reflect the negative impact of poor glycemic control on the hippocampal formation⁴.

Reproductive function and diabetes:

Both clinical and animal research have demonstrated that diabetes mellitus is commonly associated with altered thyroid, adrenal and gonadal function. Some of these changes are reversed with insulin replacement therapy, but endocrine function is not always restored to normal even with rigorous glycemic control. poorly controlled diabetes exhibit basal and stimulated growth hormone (GH) hypersecretion, and good metabolic control present with diurnal and exercise-induced GH hypersecretion. effect of diabetes appears to involve changes in hypothalamic thyrotropin-releasing hormone (TRH) secretion as well as changes in pituitary thyrotropin (TSH) release and direct effects at the level of the thyroid gland. Adrenal cortical function is often enhanced in diabetes, most likely due to alterations in glucocorticoid feedback responses. Male and female reproductive function is often disrupted in diabetes. Data from animal studies suggest that the major cause is altered hypothalamic LHRH secretion secondary to diabetes-induced changes in hypothalamic neurotransmitter metabolism⁵.

HPA axis and insulin treatment and diabetes:

In addition to plasma adrenocorticotrophic hormone (ACTH) and corticosterone, hypothalamic corticotrophin-releasing hormone (CRH) mRNA and hippocampal type 1 glucocorticoid receptor (GR1) mRNA were also upregulated in uncontrolled streptozotocin-induced diabetes. Glucagon and norepinephrine responses to hypoglycemia were not affected by diabetes or insulin treatment. In response to hypoglycemia, hypothalamic CRH mRNA and pituitary proopiomelanocortin mRNA expression increased in insulin-treated but not in untreated diabetics. In contrast, type 2 glucocortoid receptor (GR2) mRNA was not altered by hypoglycemia. despite increased basal HPA activity, HPA responses to hypoglycemia were markedly reduced in uncontrolled diabetes. The defect in CRH response could be related to the defective GR1 response. It is intriguing that insulin treatment restored the HPA response to hypoglycemia but, not the deficient epinephrine response. This is important because during severe hypoglycemia, epinephrine is an important counter regulatory hormone^6.

Hypothalamic arousal, insulin resistance and diabetes:

In health there is a rhythmicity of cortisol secretion, with a high plasticity and efficient feedback control. The endocrine abnormalities are probably responsible for the anthropometric and metabolic abnormalities. The circulatory perturbations seem to be induced by a parallel activation of the central sympathetic nervous system suggesting an ‘hypothalamic arousal syndrome’, gradually developing into an independent risk for disease. An associated cluster of environmental factors, including psychosocial and socio-economic stress, traits of depression and anxiety, alcohol consumption and smoking, all factors known to activate hypothalamic centres, has been identified. hypothalamic arousal syndrome, with parallel activation of the HPA axis and the central sympathetic nervous system, is responsible for development of endocrine abnormalities, insulin resistance, central obesity, dyslipidaemia and hypertension, leading to frank disease, including Type 2 DM⁷.

Diabetic neuropathy and HPA axis:

diabetic neuropathy is a major determinant of the basal tone of the hypothalamic-pituitary-adrenal axis in diabetes mellitus. The circadian variation for ACTH and cortisol was normal in diabetic patients. ACTH and cortisol concentrations correlated with most clinical and neurophysiological parameters of neuropathy but not with glycemic control, retinopathy, or proteinuria. Overall, the diabetic neuropathy is associated with a specific and persistent increase in the activity of the hypothalamic-pituitary-adrenal axis corticotrophin-releasing hormone (CRH)^8.

CONCLUSION:

Obesity and type 2 diabetes continue to be major public health burdens with type 2 diabetes rising in epidemic proportions. Since known risk factors do not explain all of the variance in the population, it is important to identify novel risk factors that can lead to development of new preventive measures. Chronic psychological stress and depression are associated with type 2 diabetes but the mechanism remains unclear. Neuroendocrine changes induced by these stressors, specifically activation of the hypothalamic-pituitaryadrenal (HPA) axis and sympathetic nervous system (SNS), might provide a unifying explanation^9.

REFERENCE:

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6. Chan O, Chan S, Inouye K, Shum K, Matthews SG, Vranic M. Diabetes impairs hypothalamo-pituitary-adrenal (HPA) responses to hypoglycemia, and insulin treatment normalizes HPA but not epinephrine responses. Diabetes. 2002 Jun 1;51(6):1681-9.

7. Björntorp P, Holm G, Rosmond R. Hypothalamic arousal, insulin resistance and type 2 diabetes mellitus. Diabetic Medicine. 1999 May 1;16(5):373-83.

8. Tsigos CO, Young RJ, White AN. Diabetic neuropathy is associated with increased activity of the hypothalamic-pituitary-adrenal axis. The Journal of Clinical Endocrinology and Metabolism. 1993 Mar;76(3):554-8.

9. Golden SH. A review of the evidence for a neuroendocrine link between stress, depression and diabetes mellitus. Current diabetes reviews. 2007 Nov 1;3(4):252-9.

Received on 25.01.2016 Modified on 15.02.2016

Int. J. Adv. Nur. Management. 2016; 4(3): 393-395.

DOI: 10.5958/2454-2660.2016.00070.3