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Biomedical subjects

D K Andersen

Publications and source records attributed to D K Andersen.

53 records · Page 3Linked to original sources
PubMed1984

Insulin's effect on bile flow and lipid excretion during euglycemia and hypoglycemia.

Mongrel dogs were prepared by cholecystectomy, ligation of the lesser pancreatic duct, and insertion of modified Thomas cannulas into the stomach and duodenum. When the dogs had recovered from surgery, studies were performed on them, conscious and unanesthetized after an overnight fast. The common bile duct was catheterized through the opened duodenal cannula for collection of hepatic bile. Bile flow was stabilized by the intravenous infusion of sodium taurocholate. After 2 hr of taurocholate infusion, insulin was added to the infusion and continued for the duration of the experiment. Glucose was administered intravenously during the first 120 min of insulin administration to maintain euglycemia; then the glucose was discontinued. The intravenous infusion of insulin during euglycemia maintained by glucose infusion caused a significant increase in bile flow and a decrease in bile salt concentration, but no change in bile salt output. There was a decrease in cholesterol concentration and output and in phospholipid concentration, but no significant change in phospholipid output. When glucose infusion was discontinued and hypoglycemia occurred, there was a further significant increase in bile flow, but no other change. These studies demonstrate that the choleretic action of insulin is not dependent upon hypoglycemia and that intravenously administered insulin may cause increased bile secretion without increase in serum glucagon concentration. These experiments also confirm that insulin choleresis may be associated with a decline in cholesterol output.

Animals↗
PubMed1984

Multiple pancreatic pseudocyst disease.

In an effort to determine the incidence of multiple pseudocyst disease and establish the optimal approach to this problem, the records of 91 consecutive patients diagnosed during a 36-month period as having pancreatic pseudocyst disease by sonography or computerized tomographic scanning were reviewed. Thirteen patients (14.3%) had multiple cysts; all received sonograms and six had CT scans. The combined false negative and false positive rate with sonography was 9%. Spontaneous resolution occurred involving five cysts (18%) up to 6.5 cm in size. The diagnosis of cyst multiplicity was confirmed at operation in seven cases; two of the seven operations were excisional and the remaining patients received drainage procedures. There were no operative deaths; complications included one patient who required chronic enzyme replacement therapy after excision and another patient who developed a subphrenic abscess after attempted percutaneous drainage. The incidence of multiple pseudocyst disease in our series is just over 14%. The possibility of multiplicity should be carefully investigated in each patient with pseudocyst disease. In light of the rate of spontaneous resolution, not all patients with multiple pseudocysts may require operative therapy. Because of the 7.7% false negative diagnoses with sonography, CT scanning is especially helpful when the diagnosis of multiple pseudocysts is suspected or in preoperative preparation of pseudocyst drainage. If an operation becomes necessary, a drainage procedure rather than excision should be used whenever possible to maximize gland salvage.

Adult↗
PubMed1984

The hepatic extraction of gastric inhibitory polypeptide and insulin.

The hepatic extractions of gastric inhibitory polypeptide (GIP) and insulin were determined using in vitro and in vivo methods to assess the role of the liver in GIP metabolism and the possible effect of GIP on the hepatic extraction of insulin. During in vitro studies using the isolated perfused rat liver, infusion of GIP (2000 pg/ml) alone and in combination with porcine insulin (200 microU/ml) resulted in negligible hepatic extraction of immunoreactive GIP (IR-GIP) in both fed and fasted animals during either physiologically euglycemic or hyperglycemic perfusions. Hepatic extraction of insulin, however, ranged from 26-36% in fasted animals and from 7-25% in fed animals. Hepatic extraction of insulin and net hepatic glucose appearance were minimally affected by GIP. In vivo studies in awake dogs were then performed, in which simultaneous portal and peripheral venous levels of IR-GIP, immunoreactive insulin (IRI), and glucose were assessed after intraduodenal glucose administration. The portal to peripheral (PORT/PERI) venous ratio of endogenous IRI and IR-GIP reflected the findings of the in vitro studies; the PORT/PERI ratio of IRI levels rose from a basal value of 1.9 +/- 0.3 to a peak of 3.7 +/- 0.9, while the PORT/PERI ratio of IR-GIP levels rose from a basal value of 1.0 +/- 0.1 to a peak of 1.4 +/- 0.2, then rapidly returned to 1.0. The in vivo data are consistent with a continuous hepatic extraction of 40-50% of the insulin entering the liver and a negligible hepatic extraction of IR-GIP. We conclude that hepatic extraction of GIP in vitro or in vivo is minimal. In addition, while the fed state of the animal before infusion can result in changes in the in vitro hepatic extraction of insulin, GIP does not mediate these changes.

Animals↗
PubMed1984

The enteric enhancement of glucose-stimulated insulin release. The role of GIP in aging, obesity, and non-insulin-dependent diabetes mellitus.

The effect of aging, obesity, and non-insulin-dependent diabetes mellitus on glucose-stimulated gastric inhibitory polypeptide (GIP) levels was studied in 55 male subjects, ranging in age from 19 to 84 yr, and in obesity, expressed as body mass index, from 21 to 34. Studies were performed using the hyperglycemic glucose clamp technique, in which the blood glucose was maintained at 125 mg/dl above basal for 2 h. Glucose (40 g/m2 body surface) was ingested at 60 min. Plasma immunoreactive GIP (IR-GIP) did not change during intravenous (i.v.) glucose alone, but began to rise within 10 min after glucose ingestion and reached a peak at 30-40 min. Basal and stimulated IR-GIP levels were markedly elevated in diabetic subjects and modestly elevated in obese subjects, compared with appropriately matched controls. In contrast, age had little effect on plasma IR-GIP levels either in the basal state or after glucose ingestion. When IR-GIP responses to oral glucose were expressed as a relative change from basal levels, IR-GIP rose 86% in diabetic subjects and 243% in obese subjects, compared with 185% and 165% in their respective controls. IR-GIP rose 179% in young subjects and 144% in middle-aged subjects, while, in old subjects, the increase was 265%. Plasma IRI levels were reduced in the diabetic subjects, slightly elevated in obese subjects, and were similar in older and younger subjects. Beta cell sensitivity to endogenous GIP decreases with age, and is unchanged in both obesity and nonmedicated diabetes.

Adult↗
PubMed1983

Prevention of the glucose intolerance of thiazide diuretics by maintenance of body potassium.

The effect of thiazide diuretics on the glucose tolerance of seven normal men in whom potassium loss was prevented with supplementation was studied using the glucose clamp technique. An initial control 2-h hyperglycemic clamp was performed to create a square wave of hyperglycemia 125 mg/dl above basal. At 1 h, 40 g glucose/m2 body surface area was ingested. Serial insulin (IRI) and gastric inhibitory polypeptide (GIP) levels were measured as well as the level of glucose infusion necessary to maintain the stable hyperglycemic level. After the initial study, subjects were placed on a 10-day course of 100 mg hydrochlorothiazide and 80 meq potassium per day. Subjects were monitored for dietary potassium intake, urinary potassium, and sodium losses, and the replacement of potassium adjusted accordingly. A repeat glucose clamp was done on day 10. When potassium losses were prevented, thiazides induced no alterations in glucose tolerance, beta-cell sensitivity to glucose, GIP-cell sensitivity to glucose, beta-cell sensitivity to GIP, or tissue sensitivity to insulin. Two control studies in which hypokalemia was allowed to ensue after hydrochlorothiazide ingestion revealed a diminution in glucose tolerance, a consequence of diminished pancreatic beta-cell response to glucose. We conclude that the thiazide effect on glucose tolerance is a consequence of the resultant hypokalemia that the diuretic may create.

Adolescent↗
PubMed1983

Somatostatin suppression of canine fasting bile secretion.

Somatostatin, a peptide present in hypothalamus, gastric mucosa, and pancreas, suppresses several gastrointestinal functions. We evaluated the effect of graded doses of intravenous somatostatin on taurocholate-stimulated bile flow awake fasting dogs. Somatostatin doses of 1.5-200 ng . kg-1 . min-1 significantly suppressed fasting biliary flow. Biliary lipid concentration showed progressive elevations approaching 200% with 200 ng . kg-1 . min-1 somatostatin, while lipid outputs were not altered. The data suggest that somatostatin inhibited bile salt-independent canalicular or ductular secretion, because bile flow, chloride, and bicarbonate output, and the biliary clearance of erythritol were significantly reduced, while bile salt output remained unchanged. In addition, suppression of basal insulin concentration occurred at somatostatin infusion of 200 ng . kg-1 . min-1. Additional studies in anesthetized dogs demonstrated that somatostatin could suppress bile secretion without altering hepatic blood flow.

Animals↗
PubMed1982

Interaction of arginine and gastric inhibitory polypeptide on insulin release in man.

The interrelations of the insulin secretagogues, glucose, arginine (Arg), and gastric inhibitory polypeptide (GIP) were quantified in six normal young men in five sets of experiments with the hyperglycemic clamp technique (125 mg/dl above basal glucose levels for 2 h). After 60 min of intravenous glucose alone, one of the following was added: A) oral glucose (OG) (40 g/m2); B) 15 g.m-2.h-1 Arg infusion; C) 15 g.m-2.h-2 Arg infusion and OG; D) 7.5 g.m-2.h-1 Arg; E) 7.5 g.m-2.h-1 Arg and OG. The clearance rate of Arg was similar for B, C, D, and E. In all experiments, plasma GIP levels were unchanged from the basal level during the 1st h. The increases in plasma GIP levels in experiments C and E were similar to the increase when OG alone was ingested (A). When the stimulatory effect of the secretagogue(s) alone on insulin (IRI) is computed, the increase due to OG (A) and to 7.5 g.m-2.h-1 Arg (D) were similar and additive (A + D approximately equal to E). However, the stimulatory effect of 15 g.m-2.h-1 Arg + OG (C) on IRI was not significantly greater than 15 g.m-2.h-1 alone (B). The 15 and 7.5 g.m-2.h-1 Arg infusion produced different patterns of insulin and glucagon secretions. At the lower dose, the response of both hormones to Arg decreased with time. Arg and GIP act through a similar and possibly common mechanism on the beta-cell. However, only Arg was found to be alpha-cytotropic. GIP does not appear to influence the metabolic clearance of Arg. The dose-response relationships to Arg of the beta- and alpha-cell appear similar.

Adult↗
PubMed1982

Gastrointestinal complications after cardiopulmonary bypass.

Gastrointestinal (GI) complications after surgery requiring cardiopulmonary bypass (CPB) can be serious, often lethal events. In our study, from 1970 through 1981 there were 43 such complications after 5080 CPB cases (0.85%). We noted on annual persistent occurrence of approximately 1%. The overall mortality rate was 63%. The most frequent complication was hemorrhage (usually gastroduodenal). Other complications encountered were pancreatitis, cholecystitis, hyperbilirubinemia, bowel perforations or infarcts, and gastroduodenal alterations. We concluded that GI complications after CPB are associated with a high mortality rate and often occur with other complications. Careful judgment is needed for appropriate diagnosis and therapy.

Cardiopulmonary Bypass↗
PubMed1981

Selective potentiation of insulin-mediated glucose disposal in normal dogs by the sulfonylurea glipizide.

Investigative data have suggested that the extrapancreatic actions of the sulfonylureas may be paramount in their chronic antidiabetic action. The present study examines the effects of chronic sulfonylurea treatment on in vivo insulin action. Peripheral insulin levels, hepatic glucose production (Ra), and overall glucose disposal (Rd) were studied in six awake, normal dogs given both 0.5 and 1.0 mU/kg per min pork insulin for 2.5 h. This produces stable hyperinsulinemia from 15 to 150 min. Fasting euglycemia was held constant by the glucose clamp technique and averaged 99% basal glucose in all studies. Ra and Rd were determined from infusion of [3-(3)H]glucose, begun 90 min prior to insulin infusion. 10 mg of the sulfonylurea glipizide, was given daily to the test animals for the 10 to 20 d following appropriate control studies, then was withheld for 24 h, and the dogs were restudied. Glipizide treatment did not significantly alter basal glucose turnover, Ra, mean glucose values, or mean insulin levels as determined by radioimmunoassay. Increase in Rd above basal glucose turnover in response to insulin (delta Rd) was significantly (P less than 0.05) increased by glipizide treatment at both insulin dosage levels (paired analysis). At 1.0 mU/kg per min insulin, delta Rd rose from 2.6 mg/kg per min before glipizide to 6.5 mg/kg per min after glipizide treatment. At 0.5 mU/kg per min insulin, delta Rd went from 1.1 mg/kg per min before glipizide to 2.2 mg/kg per min after glipizide treatment. Glipizide treatment doubled the effects of insulin on Rd, while showing no significant effect upon insulin suppression of Ra. We conclude that a significant extrapancreatic chronic action of glipizide lies in its ability to selectively potentiate Rd.

Animals↗
PubMed1981

Discrepant performance on oral and intravenous glucose tolerance tests: the role of gastric inhibitory polypeptide.

Analysis of a large study population revealed a group of eight healthy men whose tolerance to oral glucose was markedly greater than their tolerance to iv glucose (disparate group). The physiological basis of the anomalous performance was investigated using a variation of the hyperglycemic glucose clamp technique. This technique allows separation of the effects of hyperglycemia and intestinal insulinotropic factors on B-cell response. The eight subjects with disparate tolerance tests were compared to eight healthy control subjects whose tolerances on the two tests were very similar. The disparate performers showed 1) higher basal circulating gastric inhibitory polypeptide (GIP) levels, 2) lower immunoreactive insulin (IRI) responses to hyperglycemia (iv glucose alone), 3) enhanced GIP response to oral glucose, and 4) enhanced IRI response to oral glucose. These results may be interpreted as indicating a role for GIP in the improved tolerance for oral glucose, although other unknown gastrointestinal hormones could theoretically also be involved. Enhanced release of GIP after oral glucose may compensate for the reduced IRI release in response to hyperglycemia. The mechanism underlying the enhanced GIP response in these studies remains to be explored. It will be of interest to follow these subjects to see whether their anomalous gut beta-cell balance has any long term pathogenetic implications.

Administration, Oral↗
PubMed1981

Chronic primary intestinal pseudo-obstruction.

Chronic primary intestinal pseudo-obstruction (CPIP) has received attention despite of its unclear etiology and infrequent occurrence. Recently a patient with this disorder had evidence of a primary visceral neuropathy. Reviewing the literature, we found 30 case reports of CPIP and evaluated their clinicopathologic findings. Presenting symptoms and radiologic findings were nonspecific. Esophageal motility was abnormal in 12 of 14 reports. Intestinal histopathology revealed normal muscle wall, mucosa, and ganglion cells in over 50% of reports. Only 48% of cases demonstrated clinical improvement. Thirty percent (8 of 30) ultimately died. We conclude that CPIP is a perplexing, often fatal entity that can mimic mechanical obstruction in the absence of definite etiology. Primary neurologic or muscular disease may be a possible explanation, but, as yet, definite documentation does not exist.

Adolescent↗
PubMed1980

Management of penetrating pancreatic injuries: subtotal pancreatectomy using the auto suture stapler.

Penetrating injuries of the pancreas have been accompanied by significant morbidity and mortality. A technique using the TA-55 Auto Suture Stapler (United States Surgical Corp., Stamford, CT) in patients with pancreatic trauma has been developed and employed clinically. The technical aspects of this simplified technique and its role in the prevention of postoperative complications of pancreatectomy are reviewed. This approach supports an aggressive and complete surgical evaluation of pancreatic injuries.

Adult↗
PubMed1978

Oral glucose augmentation of insulin secretion. Interactions of gastric inhibitory polypeptide with ambient glucose and insulin levels.

Gastric inhibitory polypeptide, or GIP, has been postulated as the major enteric hormonal mediator of insulin release. The release of immuno-reactive GIP (IR-GIP) after oral glucose and its role in insulin release was studied in normal men by the glucose clamp technique. In 24 subjects studied with the hyperglycemic clamp, blood glucose was maintained at 125 mg/dl above basal for 2 h via a primed-continuous IV glucose infusion coupled to a servo-controlled negative feedback system. 40 g glucose per m(2) surface area was ingested at 60 min, and the blood glucose was maintained at the steady-state hyperglycemic level. Plasma IR-GIP and insulin (IRI) levels were measured throughout the 2-h period. IR-GIP levels changed little when IV glucose alone was given; the mean basal value was 305+/-34 (SEM) pg/ml. After oral glucose, IR-GIP levels began to rise within 10 min and reached a peak within 40 min of 752+/-105 pg/ml. Plasma IRI responded initially to the square wave of hyperglycemia in the typical biphasic pattern. After oral glucose, plasma IRI levels rose strikingly above the elevated levels produced by hyperglycemia alone, reaching a peak of 170+/-15 muU/ml within 45 min. The time course of the rise in IR-GIP and IRI was nearly identical. To assess whether the maintenance of euglycemia would affect this process, the euglycemic clamp was employed in 11 subjects to maintain basal blood glucose levels during a similar 2-h study. A primed-continuous insulin infusion, with a constant rate of 120 mU/m(2) per min was given together with a servo-controlled glucose infusion. This resulted in hyper-insulinemia of approximately 300 muU/ml. Glucose was ingested by six subjects at 60 min. Plasma IR-GIP responded to oral glucose similarly to the effect seen in the hyperglycemic studies. No increase in endogenous insulin release was seen despite the increase in IR-GIP when euglycemia was maintained. However, in five of seven subjects given insulin whose blood glucose concentration rose by 20 mg/dl or more after oral glucose, there was an increase in plasma insulin concentration associated with the elevation in IR-GIP. Thus, the effect of glucose-released IR-GIP on insulin secretion is dependent upon the presence of some degree of hyper-glycemia and is not inhibited in the presence of marked hyperinsulinemia.

Adolescent↗
PubMed1971

Methamphetamine-induced insulin release.

Administration of methamphetamine or amphetamine to rats and mice produces a rapid increase in the level of immunoassayable plasma insulin not attributable to hyperglycemia. While in the mouse this release of insulin is followed consistently by a profound hypoglycemia, in the rat this response is variable. Studies in vitro demonstrate that insulin is released by a direct effect of methamphetamine on the pancreas.

Animals↗
PubMedDate not supplied

Surgery in the elderly: observations on the pathophysiology and treatment of cholelithiasis.

Biliary tract disease is particularly prevalent in older persons, and is the leading indication for acute abdominal surgery in the elderly. The complications of biliary stone disease are more insidious in the elderly, and the recognition of "symptomatic" disease is often delayed. The unreliable manifestations of biliary tract pathology result in a higher morbidity and mortality of the disease, and a large number of emergency operations. Recent studies suggest that the pathophysiology of cholelithiasis is specifically altered in the elderly. Pigmented gallstones, which are more common in the elderly, are thought to result from the action of bacterial enzymes that deconjugate bilirubin and form insoluble bile salts; bacterial contamination of the extrahepatic biliary system is more frequent in elderly patients. Gallbladder stasis may be due to age-related changes in the response of gallbladder musculature to the kinetic action of cholecystokin (CCK), possibly through a decrease in CCK receptor affinity or availability. Other hormonal factors which inhibit choleresis, such as pancreatic polypeptide, are increased with aging as well. Current efforts are being directed toward closer surveillance and discovery of cholelithiasis, and improved outcomes of therapy have been aided by the development of "minimally invasive" approaches to the treatment of cholelithiasis in the elderly.

Adolescent↗