Serum Immunoreactive Insulin Levels Research Articles

The effect of diphenylhydantoin on insulin response.

1. Serum immunoreactive insulin, glucose tolerance and growth hormone levels were estimated in healthy volunteers before and after receiving diphenylhydantoin sodium (DPH) for 14 days. 2. With a standard oral dose of DPH all subjects showed a reduced insulin response to oral glucose (11–44%). This correlated with the serum concentration of the drug, which ranged from 30.5 to 90.0 μmol/l (7.7–22.7 μg/ml). 3. Glucose tolerance remained normal and no changes in growth hormone levels were observed. 4. Different doses of DPH have been employed in the treatment of insulinoma and as a screening test for detecting latent insulin secretory defects. This study confirms the wide inter-individual variation in the metabolism of DPH, and stresses both the importance of measuring the serum concentration of DPH and the comparative irrelevance of dosage levels in these situations.

The effect of chronic prolactin administration upon the blood sugar, insulin and free fatty acid response to a glucose load in the dog

The effect of chronic prolactin treatment on blood sugar, serum immunoreactive insulin and free fatty acid levels has been studied in normal dogs in the post-absorptive condition and during an i.v. glucose tolerance test. It was observed that: 1) the chronic administration of prolactin failed to affect either blood sugar or serum immunoreactive insulin levels in these animals in the post-absorptive condition and induced a very minor non-significant increase in serum free fatty acid concentration; 2) although prolactin chronic administration induced a moderate reduction in the blood sugar response in the first fifteen min after the glucose load, the average glucose level, kglucose, and serum IRI profile were unaffected; 3) prolactin administration slightly accelerated the fall of FFA levels during glucose administration as well as the return to baseline values in spite of the high blood glucose and insulin levels. In dogs having undergone chronic prolactin treatment the serum FFA concentration was higher than in non injected animals in the final stages of the test, i.e. at the moment when blood glucose and insulin had returned to basal levels. The physiological significance of these changes is discussed.

Effects of an oral glucose load on serum immunoreactive insulin, free fatty acid, growth hormone and blood sugar levels in young and elderly subjects.

ABSTRACTIn 29 healthy young adults and 22 ambulatory elderly subjects, a study was made of the effects of an oral glucose load on the levels of serum immunoreactive insulin (IRI), free fatty acids (FFA), growth hormone (HGH) and blood glucose. In the elderly, the pre‐load blood glucose and serum IRI levels were higher than in the younger group, reached the peak more gradually, and took longer to return to the baseline values. There was no significant difference in the serum FFA levels between the two groups until 3 hours after the glucose load, at which time the FFA values had returned to the fasting level in the young subjects but remained depressed in the elderly subjects. Serum HGH fasting levels in the elderly males were significantly higher than in the younger males and remained so at 1–2 hours after the glucose load. For the females, the numbers were too small and the intragroup variability too great to permit drawing conclusions. The total findings lend support to Dilman's hypothesis of a genetically programmed elevation of the hypothalamic threshold to feedback suppression, with age.

Effects of adrenalectomy on the obese-hyperglycemic syndrome in mice (gene symbol ob).

Mice with the inherited obese-hyperglycemic syndrome (gene symbolob) and their lean litter mates were adrenalectomized and then studied for up to 30–36 weeks with regard to their body weights and the serum glucose and immunoreactive insulin level. Sham operated obese and lean mice were used as controls.-Adrenalectomy did not prevent the excessive weight gain of the obese mice. However, during the first three weeks after adrenalectomy the mean weight increase was some-what smaller than in the sham operated controls. The increase in the body weights of the lean animals was, however, not affected. The most prominent finding after adrenalectomy was a decrease of the serum levels of glucose and insulin in both obese and lean animals.-The results indicate that in the obese mice adrenalectomy decreases the pronounced insulin resistance. It is also suggested that insulin resistance may be dissociated from the development of obesity in these animals.

BECKWITH'S SYNDROME WITH EXTREME ORGAN HYPERPLASIA

A large newborn infant with hemihypertrophy, omphalocele, hepatomegaly, left upper quadrant abdominal mass, and zoster-like skin rash had severe hypoglycemia at 4 hours of age. Serum immunoreactive insulin levels were markedly elevated. Hypoglycemia was not controlled by vigorous medical therapy but blood glucose levels returned toward normal following subtotal excision of the markedly hyperplastic pancreas at 24 days of age. At 4½ months of age, a right upper quadrant abdominal mass was noted and urinary adrenal steroid levels were elevated. The right adrenal gland was found to be markedly hyperplastic and it was removed; the left adrenal gland was slightly hyperplastic. Between the ages of 5 and 8 months the umbilical stump enlarged progressively forming a large pedunculated tumor which was removed. This patient presents an unusually severe example of Beckwith's syndrome with both prenatal and postnatal organ overgrowth, severe hypoglycemia and hyperinsulinism.

Genetic selection for high and low fasting blood glucose levels in mice. I. Fasting blood glucose levels, glucose tolerance and isolated tissue studies.

Swiss-Hauschka mice have been selected for high (HG) and low (LG) fasting blood glucose (FBG) levels for four generations. All matings were brother to sister. Differences in mean FBG levels have remained relatively constant (20 to 30 mg%) between the two lines since initiation of selection (p<0.001). Body weights have declined more rapidly with inbreeding in the LG line as compared to the HG line through F3, but no further decline was noted in the F4 generation. Fasting serum immunoreactive insulin (IRI) levels were variable and mean levels for the two lines did not differ significantly. A comparison of glucose tolerance data between F3 HG and LG line animals showed generally higher mean glucose levels in the HG line in both fasted and randomfed states. The mean delta glucose levels during the test, however, were nearly identical in both lines. A dietary influence on glucose tolerance was shown. Severalin vitro tissue studies revealed no significant differences in hepatic glycogen and pancreatic insulin content between HG and LG line animals. Isolated tissue sensitivity to insulin appeared indistinguishable between the lines; however, hepatic gluconeogenesis and retinal glucose-6-14C oxidation rates in HG line mice may be enhanced.

The decline in pancreatic insulin release during hemorrhagic shock in the baboon.

Hyperglycemia has been noted in man and animal during hemorrhagic shock. Studies in the dog demonstrated that this hyperglycemia is accompanied by elevated levels of serum immunoreactive insulin, suggesting increased insulin resistance (2). However, recent shock studies by Carey (3) in man, and from our laboratory in the baboon (6) have shown a different pattern. Insulin levels have been depressed despite hyperglycemia, suggesting suppression of insulin release rather than increased insulin resistance.KeywordsPortal VeinInsulin ReleaseHemorrhagic ShockIncrease Insulin ResistanceAnimal EffectThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abnormalities of carbohydrate and lipid metabolism in experimentally induced acute uremia.

The effects of acute uremic syndrome on serum glucose, insulin, triglycerides and cholesterol were studied in the fasted rat 24 h following bilateral nephrectomy. The mean levels of serum glucose and immunoreactive insulin (IRI) as well as insulin to glucose ratio were significantly higher in the uremic animals than in the shamoperated controls. The fasting hyperglycemia in the presence of high levels of circulating IRI observed in the nephrectomized rats reflects a decrease in the efficiency of insulin-mediated glucose transport. The acutely anephric rat develops both significant hypertriglyceridemia and hypercholesterolemia, accompanied by a prominent increase in all lipoprotein classes. The generalized nature of the hyperlipoproteinemia as well as the lack of any positive correlation between serum lipids and circulating IRI or insulin to glucose ratio suggest that the observed hyperlipidemia must be attributed to factors other than hyperinsulinemia or insulin insensitivity alone.

Hormone fuel interrelationships during alcohol hypoglycemia in man.

SummaryBasal serum immunoreactive insulin (IRI) levels fell promptly and in parallel with the decline observed in circulating glucose levels when alcohol was administered intravenously to fasting man. Hypoglycemia and the decrease in basal insulin secretion were associated with an initial transient increment in growth hormone levels and sustained lipolysis manifested by increased free fatty acid, glycerol and acetoacetate concentrations. These findings may result from activation of the sympathetic nervous system which is known to be operative in other hypoglycemic states.

Relationship Between Differential Responsiveness of Pancreatic β Cells and the Circadian Variation of Serum Immunoreactive Insulin Levels

Serum IRI levels and insulin release in vitro were studied in normal mice during a 24–hr period. It was observed that both parameters present a clear circadian rhythm with a coincidence in the location of their highest and lowest values. These values rose from the 00–hr to the 20–hr time—points. On the basis of the coincidence of these rhythms we suggest that the changes observed in the beta cell secretory response could be the main factor responsible for the circadian rhythm in serum IRI levels.(Endocrinology 91: 738, 1972)

Ventrolateral hypothalamic lesions in obese-hyperglycemic mice (obob).

Bilateral electrolytic lesions were induced on the ventrolateral nucleus (VLN) of obese-hyperglycemic mice (obob) and lean littermates, with or without previous body weight reduction. All lean animals with VLN damage died within the first four post-operative days. In contrast, all obese mice (obob) with no prior body weight reduction recovered following an initial period of aphagia and rapid body weight loss. Three out of five reducedobob mice died following VLN lesions. - Two months after the operation the body weight of all lesionedobob mice stabilized at a level significantly lower than that of the “sham” operated obese; their serum immunoreactive insulin and blood glucose levels were also lower. - These data indicate thatobob mice respond normally to bilateral lesions of VLN and that their excess adiposity, by protecting them during the early post-operative period, facilitates their recovery. The final stabilization of the body weight of lesionedobob at a level lower than that of control mice is compatible with the view that the VLN acts as the low set point controller in the regulation of body weight.

Hyperinsulinemia and insulin resistance in genetically obese rats

Serum immunoreactive insulin levels (IRI) and insulin sensitivity were studied in lean, genetically obese “fatty” rats, and rats that became obese following hypothalamic lesions. Serum IRI was increased in obese “fatty” rats at 6 wk, 4 mo, and 11 mo of age. Similar increases were observed in hypothalamic lesioned (HTL) obese rats. Histologic changes in the appearance of islet tissue were described. Insulin sensitivity was studied in both “fatty” and HTL rats after a 19-hr fast. Genetic, but not regulatory, obesity was accompanied by insulin resistance. Possible reasons for this difference are discussed.

Studies on the effect of thyroxine onin vivo insulin secretion as modified by hypophysectomy

Blood sugar and serum immunoreactive insulin (IRI) concentrations were measured in uninjected and thyroxine-injected hypophysectomized dogs as well as in untreated normal dogs. Thyroxine was used at the following two levels: 0.5 and 100 γ/kg body wt./day, for 10 days. Serum IRI levels in the dog in the post-absorptive conditions were unaffected by both treatments. Mildly subnormal blood sugar levels were detected, in the hypophysectomized dog in the post-absorptive condition and were fully corrected by thyroxine therapy (both levels). The rate of disappearance of glucose from the blood was normal in the hypophysectomized control dogs and was unaffected by thyroxine therapy. The moderate increase in the general mean of the blood sugar throughout the test found after hypophysectomy was corrected by thyroxine (low level); thyroxine therapy (high dose) not only failed to correct the increase but in fact induced a further increase. The typical slow, low and maintained insulin response to hyperglycaemia was found in the hypophysectomized control dogs, and it remained unchanged despite the thyroxine treatment (both levels). We concluded that the presence of the pituitary gland is needed so that the thyroxine-induced inhibition of the insulin secretory response to hyperglycaemiain vivo may be exerted.

Effect of age on corbohydrate metabolism.

Serum immunoreactive insulin (IRI) levels were higher in older persons initially and throughout a three-hour glucose tolerance test when 176 persons from a random sample of Sudbury, Massachusetts were tested. Multiple regression analyses indicate that the higher IRI levels are associated with the rise in blood glucose and body weight that accompanied advancing age. Consequently, the different frequency distributions of interdependent variables in various studies probably explain the contradictory results in the literature when the blood insulin changes with age are interpreted. It is concluded from this study that advancing age is accompanied by an adequate responsiveness of islet cell tissue to glucose and that the higher blood glucose levels are the primary alteration to occur. This implies an alteration of the insulin release mechanism, presumably affecting the stimulus required to initiate this complex since higher blood glucose levels are required to produce equivalent blood insulin levels when age increases.

Serum immunoreactive insulin levels during glucose tolerance and intensive islet stimulation. Effect of prednisone.

The effects of a potent glucocorticoid (prednisone) on hlood sugar and serum immunoreactive insulin (IRI) levels during glucose tolerance and intensive islet stimulation were studied in forty-two subjects whose glucose tolerance ranged from well-within-normal limits to frankly diabetic. The ability to maintain “normal” glucose tolerance under this added stress was not directly related to capacity for increasing serum IRI levels. “Diabetic” subjects were not more susceptible to degeneration of glucose tolerance after prednisone even though serum IRI levels increased little 01 even decreased in several subjects. The data make it difficult to directly relate the magnitude of serum IRI levels at the times measured to degree of glucose intolerance and suggest that other factors (possibly insulin resistance), as yet unknown, are operative.

Circadian Variation of the Serum Glucose and Immunoreactive Insulin Levels

The serum glucose and immunoreactive insulin levels were determined in mice during a 24-hr period. Both parameters showed a clear circadian rhythm, having their highest and lowest values located in the (light) and (darkness) respectively. However, they were not hourly coincident, since the glucose peak preceded the insulin peak by 4 hr. This fact is explained on the basis of hormone interaction during the day. The present results show the importance of chronobiology in endocrine studies. {Endocrinology 88:1529,1971) A LTHOUGH glucose has been pointed out as J\. the most physiological stimulus for insulin release, several other substances have been described as having such effect upon this process. Agents capable of inducing the secretion of insulin are certain aminoacids (1), short chain fatty acids (2), tolbutamide (3), glucagon (4), cyclic AMP (5). On the other hand, several hormones are able to modify the pancreatic beta cell behavior; e.g., catecholamines block the glucose-induced insulin secretion (6), whereas this secretion is enhanced in the presence of hormones like growth hormone (7) and corticoids (8). Hence, both the serum insulin levels and the pancreatic response in the whole animal must be considered a multiple-dependent process rather than a simple stimulus-secretory response interaction. On the basis of this assumption, the beta cell effect of any substance administered to an experimental animal would be conditioned by the action of the animal's intrinsic regulators at that moment. Since our main field of interest is related to the regulatory mechanisms of insulin secretion, we assumed that it should be important to study the spontaneous fluctuations of both the serum glucose and immunoreactive insulin (IRI) levels during the 24-hr period. Materials and Methods Female mice of the C3H-S strain, 10 weeks old, from the Instituto de Embriologia, Biologia e Histologia, Facultad de Ciencias Medicas, UniReceived December 4, 1970. This paper was partially supported with funds from the Consejo Nacional de Investigaciones Cientificas y Tecnicas de la Republica Argentina (Grant 3477a/69), Comisidn de Investigaciones Cientificas de la Universidad Nacional de La Plata and Comisidn de Investigaciones Cientificas de la Provincia de Buenos Aires. versidad Nacional de La Plata, were used. They were caged in a room at a temperature of 25 ± 1 C with water and food ad lib. and illumination (fluorescent light 40W) from 0600 (6 AM) to 1800 (6 PM) alternating with 12 hr darkness. Since the animals engage in exercise and food intake only during the darkness this is called the activity period, the other one being the resting period (9). This nomenclature provides an appropriate way to compare animal and human experiments. Lots of 40 animals each were bled through a retro-orbital plexus with a heparinized capillary tube at 0000, 0400, 0800, 1200, 1600 and 2000 hr on different days. The blood collected at every time point was divided into several pools in order to obtain a suitable volume for the glucose and IRI determinations. The serum obtained after centrifugation was kept frozen at — 20 C until the determinations were performed. Glucose concentration and IRI levels were determined by the Otoluidine (10) and the charcoal-dextran immunoassay method (11), respectively.

Serum immunoreactive insulin levels during glucose tolerance and intensive islet stimulation.

Glucose tolerance and intensive islet stimulation tests were done on eighty-seven subjects who covered a broad range of age and glucose tolerance. The data suggest decreasing glucose tolerance with increasing age compatible with the observations of others. Over a broad range of glucose tolerance there was seen such a broad spread of serum immunoreactive insulin levels (IRI) that it was not possible to relate them directly to the degree of glucose tolerance seen. This suggested that multiple factors, including variations in peripheral resistance to insulin not attributable to known factors, are operative in determining glucose tolerance. Only when glucose tolerance was very abnormal or fasting blood sugar was elevated was there apparent decrease in serum IRI response to the stimuli used, making it difficult to attribute mild-to-moderate degrees of glucose intolerance to lack of capacity for IRI release. A close correlation between the two-hour IRI in a glucose tolerance test and the levels obtained after the stimulus of glucagon and tolbutamide suggested that the former may be an adequate reflection of islet secretory capacity.

Feeding behavior of monkeys: Glucose utilization rate and site of glucose entry

Hypoglycemia can induce hunger, but evidence of increased rates of glucose utilization contributing to satiety signals is tenuous. Therefore, monkeys (4.5–6.5 kg) were given 30-min injections of 0.9% NaCl on control days or glucose (5 g) into the jugular vein, mesentary vein, or stomach prior to daily 2-hr feedings. In spite of high levels of serum glucose, immunoreactive insulin and glucose utilization rate prior to and during initial stages of the feeding period, food intake was essentially not decreased. A similar pre-feeding load of 25 g into the stomach was also ineffective. However, if 25 g were given during the first 30 min of the feeding, the monkeys ate very little after 30 min, total depression, 60 per cent. Thus, high levels of glucose and glucose utilization alone are not sufficiently strong satiety factors in monkeys to reduce food intake of a single daily meal. However, if gastrointestinal glucose loads accompany oral feeding, intake of a scheduled meal is greatly suppressed. It is not clear what mechanism sensitizes the satiety receptor system to these signals of glucose metabolism.

Rats enriched with odd-carbon fatty acids. Effect of prolonged starvation on liver glycogen and serum lipids, glucose and insulin.

Male rats were fed a complete diet containing 30 per cent of calories as fat, with corn oil exclusively in the controls and a 7:3 mixture of triundecanoin (C11) and corn oil in the experimental group. After six weeks, rats were sacrificed in the fed state and at 24, 48, 96 and 144 hours of starvation. In the experimental group, adipose tissue fatty acids were enriched with undecanoate to an average of 28 per cent of total fatty acids. Serum glucose was found to be significantly higher in the experimental group at all periods of starvation, and liver glycogen in the experimental rats was significantly higher at 48, 96 and 144 hours of starvation. Planimetry of the area circumscribed by values plotted from 24 to 144 hours of starvation gave mean values of immunoreactive insulin of 22.37 mU. hours per ml. for the experimental versus 13.55 mU. hours per ml. for the control group (P &amp;lt; .005), and mean values of free fatty acids of 967 mEq. hours/L. for the experimental versus 1,128 mEq. hours/L. for the control group (P &amp;lt; .05). Weight loss and nitrogen excretion were not significantly different among the two groups, nor were levels of serum cholesterol and triglycerides. The data suggest that during prolonged starvation, the odd chain, fatty acid-enriched animals are capable of maintaining liver glycogen and serum glucose better than even-chain-enriched control animals. These changes are reflected in concurrently higher serum immunoreactive insulin and lower free fatty acid levels. The odd-chain fatty-acid-enriched rat appears to be endowed with potentially glucogenic fatty acids.

Studies on the effect of hyperthyroidism on the insulin response to hyperglycemia in the dog.

We studied the effect of hyperthyroidism on the insulin response to hyperglycemia in the dog during a standard oral (OGTT) and intravenous (IVGTT) glucose tolerance test. The development of the hyperthyroid condition was elicited through chronic subcutaneous 1-thyroxin treatment at one of the following doses: 0.5 and 100 γ/kg body weight/day, for 10-12 days. Blood sugar and serum immunoreactive insulin (IRI) were measured. Normal fasting blood sugar and serum IRI levels remained unchanged in the dog, despite the thyroxin treatment. The rate of disappearance of intravenously injected glucose from blood was normal as well. However, a shorter than normal, 50% diminished and late insulin response to glucose was found in the hyperthyroid group (both thyroxin levels). The blood sugar curve during the OGTT was found to be normal during the mild degree of hyperthyroidism, which was accompanied with an earlier than normal and moderately maintained insulin response to hyperglycemia, whose maximum was 25% above normal. The blood sugar curve during the OGTT was normal in the severely hyperthyroid dogs only for the 60 minute-period following glucose administration. However, the blood sugar was still above control levels 30 minutes later in this group. A definitely reduced (low, late and shorter than normal) insulin response to hyperglycemia was found after thyroxin treatment (high level).