Immunoreactive Insulin Glucagon Research Articles

Endocrine Function of the Pancreas and Gastrin Secretion in Patients with a Kidney Transplant<sup>1</sup>

In 24 patients with a kidney transplant and in 10 healthy subjects the test meal response of immunoreactive insulin (IRI), glucagon (IR-G), pancreatic polypeptide (IR-PP) and gastrin (IR-Ga) was studied. Patients with a kidney transplant showed significantly elevated basal plasma glucagon levels but normal levels of plasma IRI, IR-PP and IR-Ga. After administration of a test meal a significantly suppressed response of IRI, IR-PP and IR-Ga secretion was observed both in the patients treated with azathioprine as well as those treated with ciclosporin. In patients of the ciclosporin group the compromised response of IR-Ga and IRI secretion was significantly more marked than in subjects in the azathioprine group. From the results obtained in this paper it follows that the type of immunosuppressive drugs (azathioprine or ciclosporin) seems to be of minor importance in the pathogenesis of the described endocrine abnormalities.

Effects of long-term glibenclamide administration on gastrointestinal and pancreatic hormones in normal fasting rats

We previously reported that sulfonylurea treatment reduces insulin (IRI), glucagon (IRG) and somatostatin (SRIF) release following metabolic stimuli from the isolated perfused pancreas of normal rats and that a reduction in IRI, IRG and SRIF pancreatic content was also observed. The present work was undertaken to investigate the effects of long-term glibenclamide treatment on the gastrointestinal content of gut hormones in normal rats. Moreover, the effects of sulfonylurea treatment on IRI, IRG, and SRIF pancreatic content were also analyzed and compared to the peripheral hormone plasma levels. Two groups of male Sprague-Dawley rats received glibenclamide (1 mg/kg/day per os; n = 14) or placebo (distilled water; n = 10) for 5 months, respectively. Tissue contents of IRI, IRG and SRIF in acid-ethanol extracts of pancreas and of gastric inhibitory peptide (GIP), vasoactive intestinal polypeptide (VIP), entero-glucagon (gut-GLI) and SRIF in acid-ethanol extracts of intestine were determined. Blood glucose and plasma pancreatic hormone levels were also measured. Glibenclamide treatment lowered the levels of IRI, IRG and SRIF in the pancreatic tissue; in the same way gut-GLI, SRIF and VIP intestinal concentrations were significantly reduced, whereas no significant inhibition was detected in intestinal GIP content. Blood glucose levels and IRI and SRIF plasma concentrations were similar in the two groups. IRG plasma levels were reduced in the sulfonylurea group. These findings might suggest that sulfonylurea suppresses hormone biosynthesis in a non-specific manner.

The presence and actions of NPY in the canine endocrine pancreas

Immunofluorescent staining for neuropeptide Y (NPY) in canine pancreatic tissue was performed together with an evaluation of the effects of synthetic NPY on the release of insulin (IRI), glucagon (IRG) and somatostatin (SLI) from the duodenal lobe of the canine pancreas in situ. NPY-like immunoreactivity was localized in perivascular nerve fibers throughout the acinar tissue. NPY-immunoreactive fibers were also demonstrated in the islets, usually surrounding blood vessels but also occasionally in fibers associated with endocrine cells, primarily at the periphery of islets. In addition, the ganglia dispersed in the pancreatic parenchyma were densely innervated by NPY-immunoreactive fibers, and these ganglia regularly contained cell bodies staining for NPY. Direct infusion of NPY into the pancreatic artery (p.a.) produced a dose-dependent decrease of pancreatic SLI output and of pancreatic venous blood flow. Low-dose p.a. infusion of NPY (50 pmol/min) had no effect on basal IRI or IRG output or on the islet response to glucose (5-g bolus, i.v.). High-dose p.a. infusion of NPY (500 pmol/min) transiently stimulated IRI output and modestly increased IRG output. However, the comparatively sparse innervation of canine islets with NPY-like immunoreactive fibers and the relatively minor effects of large doses of synthetic NPY on pancreatic hormone release lead us to conclude that this peptide is not an important neuromodulator of islet function in the dog.

Glucose turnover in insulinoma — a case report

To define glucose flux in a state of chronic endogenous insulin excess, a patient with an insulinoma was studied. Plasma glucose, insulin (IRI), glucagon (IRG) and glucose turnover ([3-3H]glucose infusion) were measured before and after insulinoma resection in the postabsorptive state (PA), during a glucose infusion adjusted to attain euglycemia (before insulinoma resection only) and following an intravenous glucagon bolus (1 mg). Before insulinoma resection, plasma glucose was 55 mg/dl, glucose production (Ra) and disappearance (Rd) were equal (1.6 mg/kg/min) and glucose clearance was elevated (2.8 ml/kg/min) in PA. When glycemia was raised with a glucose infusion to 77 mg/dl, Rd did not change; in contrast Ra dropped to zero. Plasma IRI and IRG concentrations were 0.7 ng/ml and 110 pg/ml respectively before glucose infusion and remained constant throughout. After resection of the insulinoma, glycemia in PA was 103 mg/dl, Ra and Rd were increased slightly to 1.9 mg/kg/min while the metabolic clearance of glucose was decreased by 25% (2.1 ml/kg/min). Glucagon stimulation pre- and postinsulinoma resection resulted in significant increases in glycemia and IRI. We conclude that hypoglycemia with insulinoma is a consequence of decreased glucose production and increased glucose clearance. Hepatic sensitivity to small increments in glycemia is markedly enhanced so as to fully suppress endogenous glucose production at euglycemic levels in the absence of any change in IRI and IRG. The mechanisms controlling hepatic Ra in insulinoma appear different from normal.

Changes in plasma glucose, insulin (IRI), glucagon (IRG) and free fatty acids (FFA) following alanine loading in hyperthyroid patients.

The responses of plasma glucose, insulin (IRI), glucagon (IRG) and free fatty acids (FFA) following alanine loading (0.1 g/kg) were observed in 9 control subjects and 7 hyperthyroid patients, before and after restoration of thyroid function to normal. Despite the persistence of impaired glucose response to alanine, the blunted IRI and IRG responses in the hyperthyroid state were improved with a significant reduction in fasting IRI and IRG after treatment. Markedly increased FFA following alanine loading in hyperthyroid patients was reduced after treatment, but the FFA concentration remained greater than in the control subjects. We tentatively conclude that the impaired alpha and beta-cell responses to alanine were temporarily induced by the direct and/or indirect effects of thyroid hormone excess.

Effects of naloxone administration on endocrine abnormalities in chronic renal failure.

In 72 patients with end-stage renal failure and 70 healthy subjects, the influence of blockade of opioid receptors by naloxone on secretion of prolactin, lutropin (LH), follitropin (FSH), adrenocorticotropin (ACTH), somatotropin (HGH), insulin (IRI), glucagon (IR-G), parathyroid hormone (PTH) and calcitonin (CT) was studied. Administration of naloxone stimulated luliberin-induced LH and FSH secretion quantitatively equally in patients and controls. Blockade of opioid receptors was followed by a less marked suppression of chlorpromazine-induced prolactin secretion but by a higher response of hypoglycemia-induced ACTH secretion in uremic patients than in controls. In addition, a less marked suppressive effect of naloxone was noted on hypoglycemia-induced HGH secretion in chronic renal failure as compared with controls. Blockade of opioid receptors improved significantly glucose tolerance and glucose-induced insulin secretion in uremic patients and suppressed nearly completely glucagon secretion response during the second phase of a glucose tolerance test. Finally, administration of naloxone was followed by a blunted response of Ca-induced CT secretion and suppression of PTH. Data presented in this paper suggest the existence of hyperendorphinism in end-stage renal failure.

Effectiveness of somatostatin in regulating pancreatic splenic lobe hormone secretion following 99% pancreatectomy in adult chickens

In vivo studies were carried out in adult chickens in an attempt to evaluate the effectiveness of somatostatin (SRIF) in regulating hormone secretion from the splenic pancreatic lobe after 99% of the pancreatic mass was surgically ablated. Sixteen days after either sham operation or 99% pancreatectomy, birds were infused iv with SRIF (420 ng/min) alone and then glucose (59 mg/Kg/min) was superimposed on the infusate, or birds were infused iv with glucose alone and then SRIF was superimposed on the infusate. Serial blood samples were taken during the 16-day postoperative period and also at regular intervals during the 75-min observation period. Plasma was analyzed for glucose, insulin (IRI), glucagon (IRG), pancreatic polypeptide (IRAPP), and somatostatin (IRSRIF). Careful standardization of the SRIF radioimmunoassay, as well as analysis of the molecular form of circulating SRIF, indicated that “true” SRIF levels were being estimated in plasma of both groups of chickens. Normal-fed chickens have plasma SRIF levels of 1.12 ± 0.07 ng/ml which increases 16 days after 99% pancreatectomy to 2.39 ± 0.15 ng/ml plasma. The latter decreases by 55% with an overnight fast. Glucose infusion, superimposed upon a preexisting SRIF infusion in adult chickens, did not evoke an IRI response in the 99% depancreatized birds equal to that observed in sham-op controls. Although a full SRIF dose-response curve was not generated, the glucose data strongly suggest a reduced sensitivity of insulin-secreting cells to SRIF in pancreoprivic birds. Both bird groups were equally—and markedly—sensitive to the IRG-depressant effects of SRIF; in contrast, the depancreatized chickens were significantly more resistant to the APP-inhibitory effects of SRIF when compared to the sham-op control birds. Thus, 16 days after partial pancreatectomy, the hormone-release mechanisms appeared altered for IRI and IRAPP in response to SRIF. Data obtained when glucose infusions preceded SRIF infusions indicated that A-cell release of glucagon was much more sensitive to glucose (as a depression) in the partially depancreatized birds than in control birds. These same birds were significantly less responsive to the glucose-depressant effect on plasma APP levels. Thus, it appears that 99% pancreatectomy increases the sensitivity of the SRIF, IRI, and IRG release mechanisms in response to glucose 16 days after surgery. The insulin-to-glucagon (I/G) molar ratios indicative of metabolic anabolism can still be achieved by nutrients 16 days after partial pancreatectomy. It is suggested that SRIF is intimately involved in the “fine tuning” of the I/G molar ratio in 99% depancreatized chickens. Whether the sensitivity alterations observed herein are reflective of receptor or postreceptor events, and whether these events take place within the splenic lobe remnant or at extrapancreatic sites, are yet to be elucidated.

The role of the splenic pancreatic lobe in regulating metabolic normalcy following 99% pancreatectomy in chickens

The functional competency of the splenic pancreatic lobe of adult chickens was evaluated by studying plasma and tissue levels of insulin (IRI), glucagon (IRG), somatostatin (IRSRIF), and avian pancreatic polypeptide (IRAPP) for 16 days following surgical removal of 99% of the pancreas. The rationale underlying this approach was to assess whether the splenic remnant tissue after 99% pancreatectomy was capable of maintaining apparent metabolic normalcy as has been suggested in the literature. Partial (99%) pancreatectomy resulted in almost immediate enlargement of the splenic remnant, immediate decreases in both plasma IRI and IRAPP, both of which subsequently reattained normal levels (IRI in 4 days and IRAPP in 16 days). Hyperinsulinemia persisted from Days 4–7 and then returned to normal the remaining 9 days. Plasma IRG levels increased markedly and progressively for the entire 16-day observation period. Plasma I/G molar ratios indicated a strong catabolic trend in the 99% depancreatized group approaching values of 0.4 by 4 hr postop, returning to normal by Day 5, only to decrease progressively again into another sustained catabolic mode of 0.8 or less for the additional 11 days. Splenic lobe hormone (total) content of IRI, IRG, and IRAPP increased significantly throughout the 16-day observation period; however, parenchymal enlargement of nonendocrine lobe tissue was so great that actual concentrations of IRI and IRG decreased significantly while IRAPP concentration appeared to remain constant at control levels. IRSRIF levels were very sensitive both to pancreatectomy (increasing 140% 16 days later) and to fasting (decreasing 52% after 48 hr). IRG levels increase with fasting and with the exception of IRAPP, pancreatectomy appeared to increase the “sensitivity” of the splenic remnant in responding to the fasting stimulus. The results suggest that very rapid enlargement of the remnant splenic lobe following 99% pancreatectomy is probably adequate to maintain an apparent metabolic normalcy in adult chickens. The depancreatized animal enters a strongly catabolic mode, due mainly to hyperglucagonemia, even though food intake is normal and body weight is constant (though at subcontrol levels) after 16 days. There is no evidence to support the suggestion that SRIF stimulates glucagon release.

Influence of protein intake on renal hemodynamics and plasma hormone concentrations in normal subjects.

Glomerular filtration rate (GFR) by clearance of inulin and creatinine and effective renal plasma flow (ERPF) by para-aminohippurate clearance was investigated in 8 normal volunteers on low protein (LP) and high protein (HP) diet for 6 days in the basal state and after a mixed protein-rich test meal. Plasma immunoreactive insulin (IRI), glucagon (IRG) and growth hormone (IRHGH) were followed before and after the test meal. GFR was higher on HP than on LP diet and increased within one hour after the test meal. ERPF also increased significantly after the meal on LP diet. IRI increased maximally at 60 min after the test meal and then declined gradually. IRG increased after a latency period of 90 min and IRHGH consistently did not change. Since the increase in GFR was significant already one hour after the test meal, i.e. before IRG was changed, we conclude that glucagon is not a mediator of the protein-induced increased in GFR. Neither insulin nor growth hormone appeared to be involved.

Rapid changes in hepatic glucose output after a pulse of growth hormone in dogs.

In response to a single intravenous injection of bovine growth hormone (GH, 100 micrograms/kg) the non-steady-state turnover of glucose, as well as portal levels of insulin (IRI), glucagon (IRG), somatostatin (SRIF), and glucose were determined in normal conscious dogs. Using the two-compartment model validated to calculate rapid turnover changes and tracer infusion methods, the rate of hepatic output of glucose [Ra(t)] was found to be increased, reaching a maximum of 224 mg/min, 7.4 times the basal rate, 4 min after injection of GH. Ra(t) returned to its basal level 35 min later in a damped oscillatory manner. Hormone determinations were carried out in portal venous blood drawn every 2 min for 2 h from an indwelling catheter. IRG peaked 2 min after GH injection and levels of IRI, SRIF, and glucose peaked between 4 and 8 min. Hormone concentrations returned to normal, i.e., were oscillating around base-line levels, about 30 min after GH. These experiments demonstrate for the first time in vivo that a pulse of GH causes transient changes of glucose turnover and measurable alterations of the hormonal homeostasis in the splanchnic area.

Fasting and postprandial plasma glucagon and glucagon-like immunoreactivity are normal in obese Pima Indians.

Glucose, insulin (IRI), glucagon (IRG) and GLI were measured in plasma samples obtained from 32 subjects representing a wide range of body weight (body mass index = 21-49 kg/m2) after an overnight fast and for 6 hr following ingestion of a standard test meal. The 6 hr integrated postprandial response of each hormone was estimated for each subject from the area of the response curve above basal concentration. Both fasting (r = 0.72, p less than 0.0001) and postprandial (r = 0.45, p less than 0.01) IRI were significantly correlated with degree of obesity, as expected. However, the fasting and postprandial plasma glucagon and glucagon-like immunoreactivity levels were not related to obesity of the subject and were not different for the obese (BMI greater than 35, n = 16) and nonobese (BMI less than 30, n = 12) groups. Thus, there is no evidence for an abnormality in the response of these peptide hormones to a mixed meal in this obese population.

A study of the structural and biochemical development of human fetal islets of Langerhans.

The structural and biochemical ontogeny of 14 mid-trimester (12.0–19.5 wk) human fetal endocrine pancreata were examined. Each pancreas was halved at the region of the isthmus into duodenal (D) and splenic (S) portions, and islets, isolated from each of the two portions, were aliquoted and grouped according to diameter into 4 categories: (1) > 300 μm (2) 300–200 μm (3) 200–100 μm (4) 100 μm. At all fetal ages, the number of islets isolated from the splenic half was greater than from the duodenal half, and the number of islets increased as their diameter decreased. The mean total cell number per islet for each of the 4 categories are reported: (1)(D) 30,810 (S) 28,450; (2)(D) 10,970 (S) 10,250; (3)(D) 3,390 (S) 3,460; (4)(D) 1,930 (S) 1,840. Measurement of islet insulin (IRI), glucagon (IRG), and somatostatin (IRS) by radioimmunoassay showed a progressive increase with time in the content of all three hormones in all islets from both halves of the pancreas (with the exception of the smallest islets of <100 μm diameter). After 18 wk, a dramatic increase in the content of all three hormones was observed particularly in the case of the largest (>300 μm) islets. In contrast, pancreatic polypeptide (IRPP) shows no significant increase. With the exception of the smallest islets (100 μm), all splenic-half islets contain a significantly greater content of IRI, IRG, and IRS compared with their duodenal-half match while the content of IRPP is significantly greater in the duodenal-half islets. In addition, all islets with the exception of the largest (>300 μm), contained equal quantities of IRG and IRS and these results were apparent at 12 wk gestation. These data provide new insights into the ontogeny of individual islet cells during the mid-trimesteric period and serve as a basis for future studies of both normal and abnormal pancreatic development.

Starvation and Age Effects on Glycoregulation and Hormone Levels of C57BL/6J ob/ob Mice

The contributions of insulin (IRI), glucagon (IRG), and corticosterone production to the glycemic changes associated with age and starvation were examined in 3 and 6 month old ob/ob and lean mice. Three month old ob/ob mice had elevated glucose levels under all feeding conditions, but in older obese mice basal hyperglycemia was evident only after 48 hours of food deprivation. These age differences in glycoregulation were not consistently related to changes of IRI, IRG, or corticosterone concentrations. Similarly, the mild diabetes associated with senescence in lean mice was only evident during food deprivation. This abnormality in glycoregulation was also independent of decreased IRI or elevated diabetogenic hormone concentrations. Our results indicate that there is no simple hormonal basis for the partial remission of diabetes in older ob/ob mice, or for the development of mild diabetes in aging lean mice. Additionally, these data suggest that the tissue 'resistance' that is associated with chronic insulin overproduction might also develop in response to persistent overproduction of other metabolically-active hormones.

Persistence of immunoreactive insulin, glucagon and pancreatic polypeptide in the plasma of depancreatized chickens.

The present study evaluates the possibility that an extra-pancreatic source of insulin exists in chickens. The effect of pancreatectomy on plasma levels of immunoreactive insulin (IRI), glucagon (IRG) and pancreatic polypeptide (IRAPP) was examined . Plasma levels of IRI, IRG and IRAPP were measured both in the basal state and after an i.v. challenge with known secretogogues at several times after pancreatectomy. The nature of the avian plasma immunoreactivity was further characterized by gel filtration. Results indicated that plasma IRI and IRG persisted for 5 h, 24 h and 5 days after pancreatectomy. Furthermore, plasma levels of IRI and IRG remained responsive to the stimulus of i.v. arginine. The Sephadex G-50 elution profiles for IRI and IRG were similar for plasma obtained from both depancreatized and intact chickens. Postmortem tissue analyses indicated that the persistence of IRI and IRG in the depancreatized animals was not due to the presence of pancreatic remnants. Plasma IRAPP decreased to undetectable levels 5h after pancreatectomy. Although plasma IRAPP was measurable 1 and 5 days after pancreatectomy, these levels were not responsive to i.v. pentagastrin. Furthermore, gel filtration experiments indicated that the only form of IRAPP remaining after pancreatectomy had an apparent mol. wt of greater than 100 000. Such a compound was not secreted by the pancreas in vitro. Evidence presented herein indicates that pancreatic polypeptide is the only pancreatic hormone to be eliminated from the circulation after pancreatectomy in chickens. It is suggested that the depancreatized chicken might be useful as a model of a 'selective pancreatic polypeptide deficiency.

Effects of glucose infusion on hepatic and muscle glycogenolysis in exercising dogs.

Hepatic glucose production (Ra) and the rate of utilization of nonglucose sources (essentially muscle glycogen) were measured in dogs running on a treadmill (15%, 133 m/min) with indwelling catheters in the jugular vein and carotid artery. A mixture of [3-3H]glucose and [U-14C]glucose was used as tracer according to the principles of the primed constant-rate infusion techniques. Glucose was infused intravenously at a rate (12 mg.kg-1.min-1) about 20% higher than the endogenous glucose Ra in exercising dogs. Glucose infusion started either at the beginning of the run or midexercise. Plasma insulin (IRI), glucagon (IRG), and cAMP levels were measured. Exogenous glucose prevented the usual decline of both plasma glucose and IRI without causing hyperglycemia. Exercise increased the molar ratio of IRG/IRI from 0.7 to 1.4, and glucose infusion lowered it to the resting value. The rise of plasma cAMP was slowed significantly. Both the hepatic glucose Ra and intramuscular glycogenolysis were strongly inhibited and the metabolic clearance rate of glucose was increased by 60-100%. The ratio of the specific activities of [14C]lactate to [14C]glucose indicated that 75-95% of the lactate turnover arose from plasma glucose. The corresponding value in the control group was 40-50%. It is concluded that in prolonged exercise the decline of both plasma glucose and insulin play a major role in preserving glucose homeostasis, by limiting the glucose uptake of the working muscle and by helping to achieve an approximately equal contribution of the liver and the muscle glycogen for the elevated glycolysis.

Energy Homeostasis in Hypopituitary Children and Controls

27 children aged 4-16 yrs with hypopituitarism were studied before (I) and after 6 months of growth hormone therapy (II) and compared with 15 endocrinologically normal children aged 2-12 yrs (8 short stature & 7 suspected hypoglycemia) (III). Plasma glucose (G), insulin (IRI), glucagon (IRG), free fatty acids (FFA) and β-hydroxybutyrate (BOH) were measured serially during a fast and following intravenous glucagon administration which terminated the fast after a maximum of 24 hrs. The mean G nadir during the fast was 51 mg% in I, 44 mg% in II and 44 mg% in III. The glucagon stimulated G rise was significant (35 mg% in I, 33 mg% in II and 35 mg% in III). The FFA concentrations at 0 time were .59, .57 & .67 meq/1 in I, II and III respectively. In all 3 groups there was a significant increase of FFA to 1.67, 1.70 & 2.06 meq/1 in I, II & III resp. There were no intergroup differences in any of these results. BOH rose equally in groups I & II. There was a significant IRG rise during the fast of 200 pg/ml in I, 197 pg/ml in II & 234 pg/ml in III. Basal IRI values and IRI responses to glucagon were not different in I & II, but significantly higher than III at both times. The higher IRI values in I & II reflect the frequently associated obesity, particularly in older children. We conclude that energy homeostasis in hypopituitarism during fasting is associated with appropriate fat mobilization, ketone production and IRG responses. In 4 patients in I & 2 in III who became hypoglycemic (G<40 mg%) responses were similar.

Impaired alpha cell function in conditions with cortisol deficiency.

Plasma immunoreactive glucagon (IRG), insulin (IRI) and blood glucose (BG) were evaluated in the fasting state and during an arginine test (ATT) in 6 subjects with untreated hypopituitarism (H), in 2 hypopituitary subjects with normal cortisol production (H + C), in 3 subjects with Addison's disease (A) and in 14 normal volunteers (N). No increase in BG was observed in H and A after arginine, mean values being significantly lower than in N. Mean fasting and arginine-stimulated IRI levels were lower in H and A than in N; postabsorptive arginine-induced IRG levels were significantly reduced when compared to N. In contrast IRG levels in the two H + C patients were within the normal range. The impaired IRG production in A and in H (but not in H + C) suggests a close relationship between alpha pancreatic function and cortisol levels.

Glucagon release induced by ventrolateral hypothalamic stimulation in the rat.

Catheterization of the portal vein and stereotaxic implantation of electrodes in the ventrolateral hypothalamus (VLH) were performed in normal rats after thiopental anesthesia. Immunoreactive glucagon (IRG), insulin (IRI), And glucose were monitored in portal plasma before and during electrical stimulation of the VLH (6 micro A, 50 Hz, 2 msec each, for 15 min). This stimulation induced a significant and reproducible IRG rise, followed by hyperglycemia. IRI remained unchanged. These alterations were not observed in control rats, i.e. in the absence of implantation; after VLH implantation without stimulation; or after implantation in the hippocampus or in the nucleus lenticularis. Bilateral splanchnicectomy abolished the IRG rise and hyperglycemia which followed VLH stimulation, while IRI was elevated both before and during electrical stimulation. Bilateral vagotomy did not suppress the A cell response to VLH stimulation, and it significantly reduced the IRI concentration in both basal and stimulatory periods. This resulted in sustained hyperglycemia. Attempts at total denervation of the pancreas induced patterns similar to that observed after splanchnicectomy alone. These results suggest that stimulation of the VLH can influence the endocrine pancreas and blood glucose levels by sympathetic nervous inputs which stimulate A cells and inhibit B cells.

Metabolic responses to plasma concentrations of theophylline

We investigated the effect of intravenous infusions of aminophylline on plasma glucose, insulin (IRI), glucagon (IRG), growth hormone (HGH), cortisol, and free fatty acid (FFA) levels in healthy young subjects. Six received an intravenous loading dose of aminophylline (6.0 mg/kg over 20 min) followed by a maintenance dose (0.9 mg/kg/hr) for 100 min. Another 7 subjects initially received smaller loading (3.0 mg/kg) and maintenance (0.45 mg/kg/hr) doses, and after 60 min they received a second loading dose (3.0 mg/kg) followed by a larger maintenance dose (0.9 mg/kg/hr) over 120 min. In these fasting volunteers, infusion of aminophylline, which produced theophylline levels in the usual therapeutic range (10 to 20 microgram/ml) caused small increases in plasma glucose levels without changing IRI, IRG, HGH, or cortisol. There were rapid, pronounced, and prolonged rises in FFA associated with the aminophylline infusion. Increases in FFA paralleled the rise in theophylline levels. It is concluded that routine therapeutic doses of theophylline, i.e., doses that achieve serum levels normally encountered in treatment for bronchial asthma, cause a marked rise in FFA and a slight rise in glucose (8 +/- 3 mg/dl) without changing levels of IRI, IRG, HGH, or cortisol.

Glucagon-Insulin Interactions in Patients with Insulin-Producing Pancreatic Islet Lesions*

Abstract In 16 patients with benign, insulin-producing pancreatic islet cell lesions, basal plasma levels of immunoreactive glucagon (IRG), insulin (IRI), GH, and glucose were studied to assess possible interactions of glucagon and insulin in states of chronic insulin excess. Basal plasma levels of IRG were in the normal range despite hypoglycemia and hyperinsulinemia. Median plasma IRG did not correlate with median plasma total IRI (r = −0.371) or the insulin component of IRI (corrected for proinsulin proportion) (r = −0.097). Median plasma IRG and glucose correlated negatively (r = −0.617; P < 0.05). The median insulin components of IRI and glucose did not correlate (r = −0.108). When augmented hypoglycemia was induced acutely by tolbutamide, plasma levels of IRG and GH increased significantly despite concurrent exaggerated hyperinsulinemia. During 70-h fasting in one patient with insulinoma, plasma levels of IRG were not different from those observed in a healthy subject matched according to prevailing...