Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The widespread use of corticosteroids in clinical practice emphasises the need for a thorough understanding of their metabolic effects. In general, the actions of corticosteroids on carbohydrate, protein, and lipid metabolism result in increased hepatic capacity for gluconeogenesis and enhanced catabolic actions upon muscle, skin, lymphoid, adipose and connective tissues. Because of the morbidity associated with steroid therapy, the clinician must carefully consider in each case the gains that can reasonably be expected from corticosteroid therapy versus the inevitable undesirable side effects of prolonged therapy. Thus, it is important to remember that the enhanced anti-inflammatory activity of the various synthetic analogues of cortisol is not dissociated from the expected catabolic actions of glucocorticoid hormones. Replacement therapy with physiological doses of cortisol in primary or secondary adrenal insufficiency is intended to simulate the normal daily secretion of cortisol. Short term, high dose suppressive glucocorticoid therapy is indicated in the treatment of medical emergencies such as necrotising vasculitis, status asthmaticus and anaphylactic shock. With improvement of the underlying disorder, the steroid dosage can be rapidly tapered and then discontinued over a 2 to 3 day period. Long term, high dose suppressive therapy is often commonly used to treat certain diseases (see sections 4.7.2 and 4.7.3). In this setting, suppression of the hypothalamic-pituitary-adrenal axis may persist for as long as 9 to 12 months following steroid withdrawal if steroid doses are administered in the supraphysiological range for longer than 2 weeks. In general, higher doses, longer duration of usage, and frequent daily administration are all correlated with the severity of pituitary ACTH suppression. When steroid therapy is to be withdrawn, gradual tapering of the dosage is necessary; the steroid dosage should also be given as a single morning dose if possible. Rapid or total withdrawal of the steroid therapy may be associated with exacerbation of the underlying disease or with a steroid withdrawal syndrome. An additional important point to remember in any withdrawal programme is that the steroid dosage should be appropriately increased for an exacerbation of the underlying disease or for intercurrent major stress. Alternate day therapy is recommended as a steroid maintenance programme for patients requiring high dose glucocorticoid therapy over a prolonged period of time. Thus, it is usually employed to maintain a therapeutic benefit which had previously been extablished by daily steroid treatment. Complications resulting from corticosteroid therapy include: (1) proximal muscle weakness; (2) osteopenia; (3) unmasking of latent diabetes mellitus; (4) sodium retention and/or elevation of mean arterial blood pressure; (5) adverse psychiatric reactions; (6) development of glaucoma; and (7) reactivation of latent infections (such as tuberculosis).
 ...
PMID:Corticosteroids: clinical pharmacology and therapeutic use. 20 58

A patient with functioning islet cell carcinoma is described who had amelioration of her hypoglycemia during the development of ectopic ACTH syndrome. Moon facies and hyperkalemic metabolic acidosis were also present in this patient, features uncommonly seen in the actopic ACTH syndrome. At autopsy, she was found to have active tuberculosis. Prophylactic antituberculous therapy should be given to high-risk patients with the ectopic ACTH syndrome. High doses of ACTH may be palliative in refractory hypoglycemic states.
Diabetes 1975 Jun
PMID:Amelioration of hypoglycemia in a patient with malignant insulinoma during the development of the ectopic ACTH syndrome. 23

Specific neuroendocrine regulatory mechanisms in rats and mice are known to be involved in the development of pituitary tumours (prolactinomas) in systemic tolerance and carcinogenicity studies of oestrogens, certain progestagens and their combinations. However, the susceptibility of the strain used seems to be of decisive importance. High doses of oestrogens may also, in special cases, stimulate development of PRL cell hyperplasia and tumours in humans. In other species such as the hamster long-term treatment with oestrogens results in hyperplastic and neoplastic changes in MSH-producing cells of the pars intermedia of the pituitary gland. On the other hand, in the dog and monkey, steroid-related pituitary tumours were not observed, in spite of long-term treatment with high doses of oestrogens, progestagens and their combinations. The capability of certain progestagens to stimulate canine GH secretion seems to play a major role as mediator of the species-specific progestagen-induced changes (mammary tumours, diabetes- and acromegalic-like syndrome) in the beagle dog. These progestagens also seem to have, in addition to their antigonadotrophic properties, an inhibitory effect on CRH-ACTH and TRH-TSH activity in the beagle bitch. These effects can be demonstrated in both the hypothalamic-pituitary system and in the corresponding peripheral target organs. These findings in the dog were not comparable to the situation in other species including man. The extent to which all these results in different species are applicable to other species depends on whether their neuroendocrine control systems are qualitatively and/or quantitatively similar. The physiological significance of the different pituitary hormones, sensitivity of target organs as well as a certain genetic disposition in the different species should also be considered. All these factors can vary from species to species. From these facts, it can be easily appreciated that results of experiments on different species with a substance possessing the same quality of biological effect in these species (e.g., oestrogen, progestagen, etc.) can only be compared when the experimental procedure takes account of the effect of this substance on the neuroendocrine system of the different species, and when dosage, mode of administration and period of treatment are correspondingly matched to the physiological conditions of each species.
 ...
PMID:Evaluation of effects of sexual steroids on the hypothalamic-pituitary system of animals and man. 38 May 19

A study was made of the influence of somatotropic hormone of the hypophysis (STH) on the C14-glucose transport and on the C14-glucose incorporation into the glycogen of the incubated diaphragm of intact rats (group 1), hypophysectomized rats (group 2), rats with alloxan diabetes (group 3), and rats with combined exclusion of the hypophysis and the pancreas functions (group 4). The diaphragm of hypophysectomized rats had an increased capacity to the C14-glucose uptake from the medium and of incorporating it into glycogen, apparently on account of exclusion of the hormones group depending on the hypophysis, with the contrainsular action (STH, ACTH, TTH). On the contrary, the basal rate of the processes studied in the muscles of insulin-deficient rats (group 3) displayed a significant reduction. Alloxan exclusion of the B-cell function in the hypophysectomized rats (group 4) diminished the accelerated glucose transport and glycogen synthesis in the muscle. STH added to the incubation medium stimulated the glucose transport and the glycogen synthesis in the diaphragms of animals with altered endocrine homeostasis (groups 2, 3, 4). Muscles obtained from intact animals were refractory to the STH action. The most STH-sensitive were muscles of hypophysectomized animals (an increase of glucose absorption by 32%, and of C14-glucose incorporation--by 77%). Incubation of the muscles of rats suffering from alloxan diabetes with STH was also accompanied by increased rate of glucose transport and glycogen synthesis; this effect was less pronounced, however. The data obtained indicated that the regulation of carbohydrate metabolism in the muscle tissue with STH was individual, not mediated through any other hormone.
 ...
PMID:[Somatotropin control of glucose transport and glycogen biosynthesis in the incubated diaphragm of hypophysectomized rats and rats with alloxan diabetes]. 46 84

Interrelations among plasma renin activity (PRA), aldosterone and cortisole levels, 0lood volume, exchangeable sodium, urinary catecholamines, and blood pressure were studied in 35 normal subjects and 60 age-matched non-azotemic patients with diabetes mellitus (60% with hypertension, 15% with orthostatic hypotension). Basal PRA, plasma aldosterone, cortisol, blood volume, plasma potassium, and urinary electrolytes were comparable in diabetic and normal subjects. Diabetic patients, however, had a 10% increase in body sodium (P less than 0.01), and 8% of them showed normal postural PRA responses and subnormal aldosterone responses; 22% had subnormal PRA and normal aldosterone responses, and 17% had subnormal responses of PRA and aldosterone. Non-PRA-related aldosterone responses could not be explained by ACTH or electrolytes. Orthostatic decreases in blood pressure correlated (P less than 0.01) with both catecholamine excretion and basal PRA. This suggests that in diabetes mellitus, body sodium is increased. Basal PRA and plasma aldosterone are usually normal, but their postural responses are frequently impaired. Absent aldosterone responses, despite normal PRA responsiveness, may reflect an adrenal abnormality or an ineffective form of renin. Marked postural aldosterone stimulation, unrelated to PRA, ACTH, or electrolytes, points to a potent unknown factor in aldosterone control. Low levels of free peripheral catecholamines and PRA may be complementary factors contributing to postural hypotension.
 ...
PMID:Sodium, renin, aldosterone, catecholamines, and blood pressure in diabetes mellitus. 60 91

Hypoglycemia (h.) in the postneonatal period was predominantly observed in male infants and children. The incidence was 0,51/1000 hospitalizations. The majority of cases was found in the agegroup around 2 years. Concomitant diseases (mostly infections of the upper respiratory tract or gastrointestinal tract) were found in 30 out of 43 hospitalizations. Convulsions and coma were the most frequent symptoms which were found in 43%. In 30% some degree of somnolence was obvious. Hypoglycemia was not considered in the differential diagnosis in any case by the physician treating first. Only 7 out of 34 cases a complicated biochemical work up resulted in an etiological diagnosis: one leucininduced h.; one ketotic h,; one h. in dystrophy and bronchopneumonia with septicemia; one h. in meningococcic septicemia; one h. in adrenal insufficiency; one h. in isolated ACTH-deficiency; one ethyl-induced h.; one h. in polynesy of pancreas; one h. in insulinoma; one h. in diabetes mellitus under insulintherapy.
 ...
PMID:[On the syndrome of childhood-hypoglycemia. II. Hypoglycemia in the postneonatal period (author's transl)]. 89 35

A single s.c. injection (10 mg/100 g bw of alloxan) was given to nonarteriosclerotic, virgin, Sprague--Dawley rats and to breeder rats with preexisting arteriosclerosis, hyperlipidemia and hyperglycemia. All of the animals promptly developed severe diabetes with ketosis, hyperglycemia, and hyperlipidemia. Insulin therapy was deliberately withheld. Mortality was high. Seven days later one group was subjected to hypophysectomy and 30 days later, all of the animals were autopsied. The diabetes + hypophysectomy animals maintained their body weight better, did not have hypertrophied adrenal glands, showed the least elevation of serum enzymes, e.g., CPK, SGOT, SGPT and LDH, less hyperlipidemia and hyperglycemia and reduced corticosterone production than the animals with untreated severe diabetes. Despite the relative amelioration of metabolic derangements prognostic of cardiovascular degenerative changes, the diabetes + hypophysectomy animals manifested extensive renovascular damage and the breeder rats with pre-existing arteriosclerosis showed definite exacerbation of their arterial disease in response to the severe alloxan diabetes regardless of hypophysectomy. It is suggested that although hypophysectomy may alleviate certain metabolic derangements attributed to growth hormone, ACTH and adrenal steroids, the angiopathic damage proceeds inexorably.
 ...
PMID:Effects of hypophysectomy on alloxan-diabetic, arteriosclerotic, breeder vs. non-arteriosclerotic, virgin rats. 98 94

The adrenal function in diabetes mutant mice with misty coat colour (dbm) was investigated by measurements of serum corticosteroids, adrenal weights and adrenal corticosteroid content. Furthermore, the adrenal corticosteroid content was studied in obese-hyperglycemic mice (ob). In the dbm-mice the serum corticosteroid levels were elevated at the age of 5 and 12 months although the adrenal weight only was significantly elevated at the age of 5 months. The adrenal corticosteroid content was significantly lower in the 12 months old dbm-mice. In the ob-mice the adrenal corticosteroid content was elevated at the age of 5 weeks, 5 and 12 months. It is concluded that in both the dbm-mouse and the ob-mouse there is an increased functional activity of the adrenal cortex which may reflect a pituitary hypersection of ACTH, perhaps as a manifestation of a common hypothalamic disorder.
 ...
PMID:Adrenal function in the diabetic mutant mouse (gene symbol dbm). 99 90

Two patients with acromegaly have been treated with hypophysectomy. Because the disease was still active, the patients were reoperated. No pituitary tissue could be found at the second operations. Besides the acromegaly, one of the patients had diabetes mellitus (appeared after the first operation), Cushing's syndrome, probably ACTH-dependent, and evidence of thyrotoxicosis. In both patients extopic pituitary tissue was suspected. One of the patients reacted with a normal fall in plasma growth hormone to growth hormone releasing-inhibiting hormone. Ectopic pituitary function should be suspected, if the pituitary function is retained after a hypophysectomy.
 ...
PMID:Ectopic pituitary function. 118 87

Urine from 5 patients with congenital generalized lipodystrophy has been fractionated by protein precipitation and Sephadex gel filtration. A fraction with a molecular weight in the range of 1000 was observed to be metabolically active in mice, rats, and rabbits. Hypophysectomized rats got hypoglycaemia following an injection, and the lipolytic-hyperglycaemic effect of ACTH was reduced after injection into intact mice. This effect was probably due to insulin release, because no insulin-like activity was observed on isolated fat cells in vitro. Persistant changes were observed in the animals after 3 weeks of daily injections of the urinary fraction. Adult mice and rabbits developed lipoatrophy with decrease of body weight in spite of a doubling of the food consumption. The metabolic rate and the body temperature were raised. Infantile animals developed a lipodystrophic state with increased growth velocity, and 50 per cent increase of the body weight, although no fat depots were observed. The treated animals got hyperglycaemia, hypertriglyceridaemia, hyperinsulinaemia, and insulin resistance. The rabbits developed manifest diabetes. The corresponding fraction prepared from the urine from the lipoatrophic rabbits produced lipoatrophy after injection into the mice. It is suggested that the lipodystrophic urinary fraction is of hypothalamic origin, and that it acts through the pituitary gland. The fraction is still heterogenous, and was observed to contain thyrotrophin releasing activity.
 ...
PMID:Lipoatrophy produced in mice and rabbits by a fraction prepared from the urine from patients with congenital generalized lipodystrophy. 124 74


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>