Hypothalamic-Pituitary-Adrenocortical Activity in Patients With Diabetes Mellitus

Cameron, Oliver G.; Kronfol, Ziad; Greden, John F.; Carroll, Bernard J.

doi:10.1001/archpsyc.1983.01790220080013

Cited by 148 publications

(86 citation statements)

References 47 publications

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“…Second, the changes in endocrine systems caused by diabetes may affect the function of 5-HT 1A receptors. Type 1 and type 2 diabetes cause hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis in humans (Cameron et al, 1984;Roy et al, 1990Roy et al, , 1993 and animals (Scribner et al, 1991;Takao et al, 2000). In consistent with these previous reports, diabetic mice showed the increases in plasma corticosterone levels in our present result.…”

Section: Discussionsupporting

confidence: 93%

Diabetes Attenuates the Antidepressant-Like Effect Mediated by the Activation of 5-HT1A Receptor in the Mouse Tail Suspension Test

Miyata

Hirano

Kamei

2003

Neuropsychopharmacol

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Several lines of evidence have indicated that the prevalence of depression in diabetic subjects is higher than that in the general population, however, little information is available on the effects of antidepressants in diabetes. In the present study, the antidepressantlike effect mediated by the activation of 5-HT 1A receptors was examined using the tail suspension test in streptozotocin-induced diabetic mice. Long-lasting increases in 5-HT turnover rates were observed in the diabetic mouse midbrain and frontal cortex, but not in the hippocampus. Duration of immobility was significantly longer in diabetic than in nondiabetic mice in the tail suspension test. The 5-HT 1A receptor agonist ( 7 )-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (3-30 mg/kg, i.p.) reduced the duration of immobility in nondiabetic mice, and this effect was completely antagonized by pretreatment with, a selective 5-HT 1A receptor antagonist. In contrast, 8-OH-DPAT (3 mg/kg-3 mg/kg, i.p.) was ineffective in diabetic mice. The selective 5-HT reuptake inhibitor fluoxetine (3-56 mg/kg, i.p.) reduced the duration of immobility in both nondiabetic and diabetic mice. However, fluoxetine was less effective in diabetic mice than in nondiabetic mice. WAY-100635 (30 mg/kg, s.c.) reversed the suppression of the duration of immobility by fluoxetine (30 mg/kg, i.p.) in nondiabetic mice. On the other hand, the anti-immobility effect of fluoxetine (56 mg/kg, i.p.) was not antagonized by WAY-100635 (30 mg/kg, s.c.) in diabetic mice. The selective 5-HT 2 receptor antagonist 6-methyl-1-(1-methylethyl)-ergoline-8b-carboxylic acid 2-hydroxy-1-methylpropyl ester (LY53,857) (30 mg/kg, s.c.) reversed the anti-immobility effect of fluoxetine in both nondiabetic and diabetic mice. Spontaneous locomotor activity in diabetic mice was not different from that in nondiabetic mice. 8-OH-DPAT (30 mg/kg, i.p.), but not fluoxetine, increased the spontaneous locomotor activity in both nondiabetic and diabetic mice. The number of 5-HT 1A receptors in the mouse frontal cortex was unaffected by diabetes. Plasma corticosterone levels in diabetic mice were significantly higher than that in nondiabetic mice. These results suggest that the antidepressant-like effect mediated by 5-HT 1A receptors may be attenuated by diabetes.

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Section: Discussionsupporting

confidence: 93%

Diabetes Attenuates the Antidepressant-Like Effect Mediated by the Activation of 5-HT1A Receptor in the Mouse Tail Suspension Test

Miyata

Hirano

Kamei

2003

Neuropsychopharmacol

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“…In particular, some studies reported in these subjects an elevation of ACTH (10,12), basal (9 -11) and after dexamethasone test serum cortisol (13,14), and late-night salivary cortisol levels (15). In contrast, other previous studies (16 -17) did not show any alteration of pituitary-adrenal axis secretion.…”

Section: Diabetes Care 30:83-88 2007mentioning

confidence: 99%

Cortisol Secretion in Patients With Type 2 Diabetes

et al. 2007

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OBJECTIVE -The presence of an enhanced cortisol secretion in patients with type 2 diabetes is debated. In type 2 diabetic subjects, cortisol secretion was found to be associated with the complications and metabolic control of diabetes. We evaluated cortisol secretion in 170 type 2 diabetic subjects and in 71 sex-, age-, and BMI-matched nondiabetic subjects. RESEARCH DESIGN AND METHODS-In all subjects, we evaluated ACTH at 8:00 A.M. in basal conditions and serum cortisol levels at 12:00 P.M. (F24) and at 9:00 A.M. after a 1-mg overnight dexamethasone suppression test and 24-h urinary free cortisol (UFC). In diabetic patients, we evaluated the presence of chronic complications (incipient nephropathy, asymptomatic neuropathy, background retinopathy, and silent macroangiopathy). Patients were subdivided according to the absence (group 1, n ϭ 53) or presence (group 2, n ϭ 117) of diabetes complications.RESULTS -In group 2, UFC (125.2 Ϯ 4.6 nmol/24 h) and F24 (120.6 Ϯ 4.1 nmol/l) were higher than in group 1 (109.2 Ϯ 6.8 nmol/24 h, P ϭ 0.057, and 99.7 Ϯ 6.1 nmol/l, P ϭ 0.005, respectively) and in nondiabetic patients (101.7 Ϯ 5.9 nmol/24 h, P ϭ 0.002, and 100.3 Ϯ 5.3 nmol/l, P ϭ 0.003, respectively). In diabetic patients, the number of complications was associated with F24 (R ϭ 0.345; P Ͻ 0.0001) and diabetes duration (R ϭ 0.39; P Ͻ 0.0001). Logistic regression analysis showed that the presence of diabetes complications was significantly associated with F24, sex, duration of diabetes, and glycated hemoglobin.CONCLUSIONS -In type 2 diabetic subjects, hypothalmic-pituitary-adrenal activity is enhanced in patients with diabetes complications and the degree of cortisol secretion is related to the presence and number of diabetes complications. Diabetes Care 30:83-88, 2007I n patients with type 2 diabetes, glucocorticoid secretion has been suggested to be a possible link between insulin resistance and the features of the metabolic syndrome (hypertension, obesity, coronary heart disease, hyperlipidemia, and type 2 diabetes) (1-4). In fact, while glucocorticoid excess (overt or subclinical) has been demonstrated to lead to diabetes or to worsen metabolic control (5-7), the relationship between cortisol levels, insulin resistance, and chronic complications in type 2 diabetic patients without hypercortisolism is still a matter of debate.In past years, the hypothalamicpituitary-adrenal (HPA) axis secretion in patients with type 2 diabetes has been extensively investigated (8 -14). In particular, some studies reported in these subjects an elevation of ACTH (10,12), basal (9 -11) and after dexamethasone test serum cortisol (13,14), and late-night salivary cortisol levels (15). In contrast, other previous studies (16 -17) did not show any alteration of pituitary-adrenal axis secretion. The presence of chronic complications of type 2 diabetes (i.e., macroangiopathy, retinopathy, and neuropathy) has been associated to with HPA axis activity (9,18 -23), and an association between the degree of severity of several clinical measures of d...

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“…In patients with diabetes this hyperactivity of the HPA axis is indicated by elevated basal plasma cortisol concentrations, 1,2 increased urinary free cortisol, 3 enhanced cortisol response to CRH administration, 2,4 and a high prevalence of nonsuppression to the dexamethasone suppression test. 5,6 Likewise, in patients with abdominal adiposity the hyperactivity of the HPA axis is indicated by increased urinary free cortisol, 7 higher response to different stimulation tests 7,8 and a decrease in the inhibition of cortisol secretion by dexamethasone. 9 The causes of HPA hyperactivity in those hyperinsulinemic subjects remain obscure.…”

Section: Introductionmentioning

confidence: 99%

Hyperinsulinemia causes activation of the hypothalamus-pituitary-adrenal axis in humans

et al. 2001

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OBJECTIVE: Hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis is frequently found in hyperinsulinemic subjects, such as patients with diabetes or abdominal obesity. Here, the question has been posed as to whether hyperinsulinemia increases HPA secretory activity. METHODS: We performed paired -euglycemic and stepwise hypoglycemic (76 -66 -56 -46 mg=dl) -clamp experiments in two groups (each of 15 healthy men) at different insulin infusions rates, ie, 1.5 mU=min=kg (low-insulin condition) and 15.0 mU=min=kg (high-insulin condition). RESULTS: During the euglycemic clamp, the high rate insulin infusion increased plasma ACTH levels, whereas plasma ACTH levels remained essentially unchanged during the low-insulin condition (condition by time interaction, P ¼ 0.008). Likewise, serum cortisol levels were higher during the high-vs low-insulin condition (condition by time interaction, P ¼ 0.004). During the hypoglycemic clamp, plasma ACTH levels did not differ between the low-vs high-insulin condition, while serum cortisol levels were higher during the high-vs low-insulin condition at the beginning of the clamp (plasma glucose $ 76 mg=dl; P ¼ 0.032). CONCLUSION: Data indicate that hyperinsulinemia acutely increases HPA secretory activity in healthy men. This finding appears to be relevant to the pathogenesis of many clinical abnormalities associated which diabetes and abdominal adiposity, often referred to as the metabolic syndrome.

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Hypothalamic-Pituitary-Adrenocortical Activity in Patients With Diabetes Mellitus

Cited by 148 publications

References 47 publications

Diabetes Attenuates the Antidepressant-Like Effect Mediated by the Activation of 5-HT1A Receptor in the Mouse Tail Suspension Test

Diabetes Attenuates the Antidepressant-Like Effect Mediated by the Activation of 5-HT1A Receptor in the Mouse Tail Suspension Test

Cortisol Secretion in Patients With Type 2 Diabetes

Hyperinsulinemia causes activation of the hypothalamus-pituitary-adrenal axis in humans

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