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Biomedical subjects

R Gingerich

Publications and source records attributed to R Gingerich.

At least 19 recordsLinked to original sources
PubMed2001

Glucagon-like peptide-1 (7-37) augments insulin-mediated glucose uptake in elderly patients with diabetes.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) is an intestinal insulinotropic hormone that augments glucose-induced insulin secretion in patients with type 2 diabetes. It has also been proposed that a substantial component of the glucose-lowering effects of GLP-1 occurs because this hormone enhances insulin-mediated glucose disposal. However, interpretations of the studies have been controversial. This study determines the effect of GLP-1 on insulin-mediated glucose disposal in elderly patients with type 2 diabetes. METHODS: Studies were conducted on 8 elderly patients with type 2 diabetes (age range, 76 +/- 1 years; body mass index, 28 +/- 1 kg/m(2)). Each subject underwent two 180-minute euglycemic (insulin infusion rate, 40 mU/m(2)/min) insulin clamps in random order. Glucose production (Ra) and disposal (Rd) rates were measured using tritiated glucose methodology. In one study, glucose and insulin alone were infused. In the other study, a primed-continuous infusion of GLP-1 was administered at a final rate of 1.5 pmol x kg(-1) x min(-1) from 30 to 180 minutes. RESULTS: Glucose values were similar between the control and GLP-1 infusion studies. 120- to 180-minute insulin values appeared to be higher during the GLP-1 infusion study (control, 795 +/- 63 pmol/l; GLP-1, 1140 +/- 275 pmol/l; p = not significant [NS]). The higher insulin values were largely due to 2 subjects who had substantial insulin responses to GLP-1 despite euglycemia and hyperinsulinemia. The 120- to 180-minute insulin values were similar in the other 6 subjects (control, 746 +/- 35 pmol/l; GLP-1, 781 +/- 41 pmol/l; p = NS). Basal (control, 2.08 +/- 0.05 mg/kg/min; GLP-1, 2.13 +/- 0.04 mg/kg/min; p = NS) and 120- to 180-minute (control, 0.50 +/- 0.18 mg/kg/min; GLP-1, 0.45 +/- 0.14 mg/kg/min; p = NS) Ra was similar between studies. The 120- to 180-minute Rd values were higher during the GLP-1 infusion studies (control, 4.73 +/- 0.39 mg/kg/min; GLP-1, 5.52 +/- 0.43 mg/kg/min; p <.01). When the 2 subjects who had significant insulin responses to GLP-1 during the euglycemic clamp were excluded, the 120- to 180-minute Rd values were still higher in the GLP-1 infusion study (control, 5.22 +/- 0.32 mg/kg/min; GLP-1, 6.05 +/- 0.37 mg/kg/min; p <.05). CONCLUSIONS: We conclude that GLP-1 may enhance insulin sensitivity in elderly patients with diabetes.

Aged↗
PubMed2001

Effect of aging and diabetes on the enteroinsular axis.

BACKGROUND: The current studies were designed to examine the effect of aging and diabetes on the enteroinsular axis. METHODS: Healthy young control subjects (n = 10 young; age 23 +/- 1 years; body mass index [BMI] 24 +/- 1 kg/m(2)), healthy elderly subjects (n = 10; age 80 +/- 2 years; BMI 26 +/- 1 kg/m(2)), and elderly patients with type 2 diabetes (n = 10; age 76 +/- 2 years; BMI 26 +/- 2 kg/m(2)) underwent a 3-hour oral glucose tolerance test (glucose dose 40 gm/m(2)). RESULTS: Insulin responses were not different between young controls and elderly patients with diabetes but were significantly lower in elderly patients with diabetes and young controls than in elderly controls (young control: 178 +/- 27 pM; elderly control: 355 +/- 57 pM; elderly diabetes: 177 +/- 30 pM; p <.05 elderly control vs young control and elderly diabetes). Total glucagon-like peptide 1 (GLP-1) responses were not significantly different between young and elderly controls and patients with diabetes (young control: 15 +/- 2 pM; old control: 8 +/- 2 pM; elderly diabetes: 12 +/- 3 pM; p = ns). Active GLP-1 responses were also not different between young and elderly controls and patients with diabetes (young control: 5 +/- 1 pM; old control: 6 +/- 1 pM; elderly diabetes: 7 +/- 1 pM; p = ns). However, the difference between total and active GLP levels was significantly greater in the young controls (young control: 10 +/- 2 pM; old control: 2 +/- 2 pM; elderly diabetes: 4 +/- 2 pM; p <.05, young vs elderly). Glucose-dependent insulinotropic polypeptide responses were not different between young and elderly controls and between elderly controls and patients with diabetes but were significantly higher in elderly patients with diabetes than in young controls (young control: 97 +/- 12 pM; elderly control: 121 +/- 16 pM; elderly diabetes: 173 +/- 27 pM; p <.05, young vs elderly diabetes). Glucagon responses were reduced in elderly controls but were similar in young controls and elderly patients with diabetes (young control: 15 +/- 1 pM; elderly control: 9 +/- 1 pM; elderly diabetes: 16 +/- 1 pM; p <.01 elderly control vs young control and elderly diabetes). Dipeptidyl peptidase IV levels were lower in both elderly controls and patients with diabetes when compared with young controls (young control: 0.17 +/- 0.01; elderly control: 0.15 +/- 0.01; elderly diabetes: 0.15 +/- 0.01 DeltaOD/20 minutes; p <.05, elderly vs young). CONCLUSIONS: We conclude that normal aging and diabetes are associated with multiple changes in the enteroinsular axis.

Adult↗
PubMed2001

Immunoneutralization of somatostatin, insulin, and glucagon causes alterations in islet cell secretion in the isolated perfused human pancreas.

INTRODUCTION: In this study, immunoneutralization of endogenous insulin, glucagon, and somatostatin with specific antibodies was used in an isolated perfused human pancreas (IPHP) model. AIMS: To study intrapancreatic cellular interactions and pancreatic hormonal secretion. METHODOLOGY: Randomized, sequential 10-minute test intervals of single-pass perfusion with each antibody were performed at 3.9 mM or 11.5 mM steady-state glucose concentrations. Somatostatin, insulin, and glucagon levels were measured in the effluent during basal and immunoneutralization intervals. RESULTS: At 3.9 mM glucose concentration, somatostatin antibody (SS-Ab) stimulated insulin and glucagon secretion, insulin antibody (IN-Ab) inhibited glucagon secretion, and glucagon antibody (GN-Ab) stimulated insulin secretion. At 11.5 mM glucose concentration, SS-Ab stimulated insulin secretion, IN-Ab stimulated glucagon and inhibited somatostatin secretion, and GN-Ab stimulated insulin secretion. CONCLUSION: The variation in hormonal responses to immunoneutralization during stimulated and nonstimulated glucose conditions suggests that a dynamic association exists between the pancreatic cells.

Adolescent↗
PubMed2001

Effect of glucagon-like peptide 1 on non-insulin-mediated glucose uptake in the elderly patient with diabetes.

An important cause of elevated glucose levels in elderly patients with diabetes is an alteration in non-insulin-mediated glucose uptake (NIMGU). Glucagon-like peptide 1 (GLP-1) is an intestinal insulinotropic hormone. It has been proposed that this hormone also lowers glucose levels by enhancing NIMGU. This study was conducted to determine whether GLP-1 augments NIMGU in elderly patients with diabetes, a group in which NIMGU is known to be impaired. Studies were conducted on 10 elderly patients with type 2 diabetes (aged 75 +/- 2 years, BMI 27 +/- 1 kg/m(2)) who underwent paired 240-min glucose clamp studies. In each study, octreotide was infused to suppress endogenous insulin release, and tritiated glucose methodology was used to measure glucose production and disposal rates. For the first 180 min, no glucose was infused. From 180 to 240 min, glucose was increased to 11 mmol/l using the glucose clamp protocol. In the GLP-1 study, GLP-1 was infused from 30 to 240 min. In a subsequent control study, insulin was infused using the glucose clamp protocol from 30 to 240 min to match the insulin levels that occurred during the GLP-1 infusion study. During hyperglycemia, GLP-1 enhanced glucose disposal (control study: 2.52 +/- 0.19 mg x kg(-1) x min(-1); GLP-1 study: 2.90 +/- 0.17 mg x kg(-1) x min(-1); P < 0.0001). Hepatic glucose output was not different between studies. We conclude that GLP-1 may partially reverse the defect in NIMGU that occurs in elderly patients with diabetes.

Administration, Oral↗
PubMed2000

The circulating hormonal milieu of the endocrine pancreas in healthy individuals, organ donors, and the isolated perfused human pancreas.

Although basal circulating levels of individual islet cell hormones have been measured, few studies compared the molar ratios of the major hormones secreted by the endocrine pancreas. This study examined the basal levels of four major islet hormones: insulin, C-peptide (C-P), glucagon (G), and pancreatic polypeptide (PP) in normal subjects, in organ donors with brain death, and in the isolated perfused human pancreas. Basal blood samples were taken from normal, fasted control subjects (NCs). Pancreata were obtained from 17 organ donors (ODs) with donor portal vein (DPV) and radial arterial (DRA) blood samples taken before organ procurement. Single-pass perfusion was performed on the procured pancreata, and after rewarming and equilibration, basal samples were collected from the splenic vein (SV) for 30 min. Radioimmunoassays of insulin, C-P, G, and PP were performed on all samples, and basal levels of all hormones were expressed as a common unit, femtomoles per milliliter. The data suggest that in the basal state, these four major islet hormones circulate in a relatively constant molar ratio. The ratio of the hormones is altered in brain death and with in vitro perfusion of the pancreas. The isolated perfused human pancreas secretes a relatively constant molar ratio of these hormones; however, this ratio is markedly different from the circulating ratio seen in either the NC group or the OD group. We conclude that a relatively constant hormonal milieu is secreted from the normal endocrine pancreas, and this hormonal milieu is altered after brain death and with isolation and perfusion of the human pancreas.

Adult↗
PubMed1997

Intraislet regulation of pancreatic polypeptide secretion in the isolated perfused rat pancreas.

The present study is to determine if intraislet insulin or somatostatin regulate pancreatic polypeptide (PP) secretion in the isolated perfused rat pancreas by infusing insulin or somatostatin antisera. Isolated rat pancreata were stimulated with either 16.7 mM glucose (G) alone, G with antisomatostatin antibody (G + SA), or G with antiinsulin antibody (G + IA). G inhibited PP secretion -22 +/- 9.5 pM below basal, a decrease of 9 +/- 6.3% (n = 6; p = NS), G + IA inhibited PP secretion -10 +/- 27.2 pM below basal, a decrease of 20 +/- 15% (n = 7, p = NS), and G + SA stimulated PP secretion 18 +/- 7.1 pM above basal, an increase of 26 +/- 5% (n = 6; p < 0.05). G stimulated insulin secretion 3,144 +/- 210 pM above basal (n = 6, p < 0.05), and G + SA stimulated insulin secretion 2,695 +/- 195 pM above basal (n = 7; p < 0.05 vs. baseline, p = NS vs. G alone). G stimulated C-peptide secretion 886 +/- 175 pM above basal (n = 6; p < 0.05), G + SA stimulated C-peptide secretion 847 +/- 102 pM above basal (n = 7; p < 0.05, p = NS vs. G alone), and G + IA stimulated C-peptide secretion 834 +/- 93 pM above basal (n = 7; p < 0.05, p = NS vs. G alone). These data demonstrate that infusion of SA results in significant stimulation of PP secretion during high-G infusion, whereas IA has no effect. Infusions of SA or IA at the doses used have no effect on G-stimulated insulin or C-peptide secretion. This suggests that intraislet somatostatin may be an inhibitory regulator of PP secretion in the isolated perfused rat pancreas.

Animals↗
PubMed1996

Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates.

We measured plasma leptin concentrations by RIA in 204 normal weight and obese subjects, aged 18-80 yr, using full-length recombinant human leptin as a standard. Fasting levels between 1.2-97.9 ng/mL were observed. The plasma leptin concentration was highly correlated with percent body fat (r = 0.710; P < 0.0001) and was 3 times as high in women as in men (17.1 vs. 5.8 ng/mL; P < 0.0001). Circulating leptin was inversely related to age and was reduced 53% in subjects over age 60 yr. A statistical model containing percent body fat, gender, and age accounted for 65% of the variance in plasma leptin levels. Leptin was not independently related to abdominal fat distribution, plasma lipids and lipoproteins, chronic energy intake, diet composition, plasma insulin, or maximum oxygen consumption. However, plasma leptin was reduced by 26% in 5 obese subjects who consumed a 1000-Cal diet for 10 days (P = 0.004). We conclude that circulating leptin rises continuously with increasing adiposity. Gender, age, and short term caloric restriction may be important secondary regulators of plasma leptin.

Adipose Tissue↗
PubMed1996

Report of the American Diabetes Association's Task Force on standardization of the insulin assay.

Recent large-scale epidemiological studies demonstrate that blood concentrations of immunoreactive insulin predict the development of NIDDM and IDDM and are associated with the risk of several degenerative diseases, such as coronary and peripheral vessel atherosclerosis, hypertension, and dyslipidemia. The reliability of these measurements is dependent on a biological assay that has not been well standardized between laboratories. Recognizing this, the American Diabetes Association organized a task force to assess comparability of blood insulin measurements between laboratories and to suggest techniques to improve comparability. The task force found that identical serum and plasma samples measured in different laboratories produced widely disparate values that were unacceptable for population comparisons. Use of a single reference standard did little to improve comparability. Assay characteristics such as linearity, recovery, accuracy, and cross-reactivity to proinsulin and its primary conversion intermediates varied among the laboratories, and they did not readily explain differences in the measurements made from assay to assay. Use of the same assay kit in different laboratories did not always ensure comparable measurements. Linear regression of assay results from one laboratory to an arbitrarily chosen reference assay greatly improved comparability and demonstrated the potential value in comparing each assay to a reference method. The task force report defines acceptable assay characteristics and proposes a three-step process of insulin assay proficiency and comparability. A central reference assay and ongoing sample exchange will be needed to allow reliable comparisons of insulin measurements made in different laboratories. Rigorous quality control and continuous quality improvement are needed to maintain reliability of the insulin measurement.

Diabetes Mellitus↗
PubMed1995

The influence of somatostatin on glucagon and pancreatic polypeptide secretion in the isolated perfused human pancreas.

The current study was undertaken to determine whether intraislet somatostatin regulates glucagon or pancreatic polypeptide (PP) secretion in the human pancreas. A high-affinity, high-specificity monoclonal somatostatin antibody (CURE.S6) was used to immunoneutralize somatostatin in the isolated, perfused human pancreas. Single-pass perfusion was performed in pancreata obtained from cadaveric organ donors using a modified Krebs media with either 3.9 or 12.9 mM glucose. Sequential test periods separated by basal periods were performed with infusion of either exogenous somatostatin-14 (SS-14), CURE.S6, or a combined infusion. Infusion of SS-14 did not significantly alter glucagon or PP secretion during low-glucose or high-glucose perfusion. Immunoneutralization of intraislet somatostatin with CURE.S6 resulted in a significant increase of glucagon secretion under low-glucose conditions (delta X = 15 +/- 3 pM) (p < 0.05), but did not significantly effect glucagon secretion under high-glucose conditions (delta X = -2 +/- 3 pM) (p = NS). PP secretion remained unchanged during CURE.S6 infusion. Combined infusion of SS-14 and CURE.S6 did not significantly alter glucagon or PP secretion. The data suggest that intraislet somatostatin may have an inhibitory role in the regulation of glucagon secretion during low-glucose conditions and that intraislet somatostatin does not regulate PP secretion in the isolated, perfused human pancreas.

Adolescent↗
PubMed1995

Higher proinsulin and specific insulin are both associated with a parental history of diabetes in nondiabetic Mexican-American subjects.

Both insulin resistance and decreased insulin secretion have been hypothesized to be precursors of non-insulin-dependent diabetes. An elevated proinsulin concentration reflects abnormal proinsulin processing and could indicate abnormal insulin secretion. We examined fasting insulin (measured by a radioimmunoassay that does not cross-react with proinsulin), as a marker of insulin resistance, and proinsulin and the fasting proinsulin-to-insulin ratio, as markers of impaired proinsulin processing, in 597 nondiabetic Mexican-Americans from the San Antonio Heart Study. Fasting insulin, proinsulin, and the fasting proinsulin-to-insulin ratio were higher in subjects with a parental history of diabetes than in subjects without such a history. These differences remained statistically significant after adjustment for obesity, body fat distribution, and glucose tolerance. A parental history of diabetes in nondiabetic Mexican-Americans is associated with an increase in fasting specific insulin and a disproportionate increase in proinsulin relative to insulin. These data suggest that both increased insulin resistance and abnormal processing of proinsulin are present in offspring of parents with diabetes.

Blood Glucose↗
PubMed1994

Use of the Fab fragment for immunoneutralization of somatostatin in the isolated perfused human pancreas.

The role of the somatostatin-secreting D cell in the islet remains controversial. The present study was undertaken to determine whether infusion of the Fab fragment of a highly sensitive somatostatin monoclonal antibody into the isolated, perfused human pancreas would influence insulin secretion. Single-pass perfusion was performed in pancreata obtained from cadaveric organ donors using a modified Krebs-media with 3.9 mM glucose. Sequential test periods separated by basal periods were performed with either somatostatin monoclonal antibody Fab fragment (SFab), somatostatin-14 (SS-14), or a combined infusion. Immunoneutralization of intraislet somatostatin with SFab resulted in a significant increase in both immunoreactive insulin (IRI) (1,122 +/- 497 pM) (p < 0.05) and immunoreactive C-peptide (IRC-P) secretion (146 +/- 53 pM) (p < 0.05). Infusion of SS-14 resulted in inhibition of both IRI secretion (-3,372 +/- 1,360 pM) (p < 0.05) and IRC-P secretion (-708 +/- 220 pM) (p < 0.05). Combined infusion of SFab and SS-14 reversed the inhibitory effect of exogenous SS-14 on IRI and IRC-P secretion. The data suggest that intraislet somatostatin has an inhibitory role in the regulation of B-cell secretion in the human islet and demonstrates that the Fab fragment of the somatostatin monoclonal antibody is an effective tool for immunoneutralization studies in the human pancreas. In addition, immunostaining of the donor pancreata demonstrated the presence of somatostatin-immunoreactive endocrine cells interspersed throughout the islet core and mantle. The demonstrated proximity of somatostatin-immunoreactive endocrine cells to B cells lends anatomic support to the concept that intraislet somatostatin influences insulin secretion in the human islet.

Adult↗
PubMed1994

Endurance exercise training improves body composition and plasma insulin responses in 70- to 79-year-old men and women.

Forty-two men and women aged 70 to 79 years were studied to assess the effects of 6 months of endurance or resistance training and subsequent cessation of training on glucose tolerance, plasma insulin responses, serum triglyceride and cholesterol levels, and plasma dehydroepiandrosterone (DHEA) levels. The endurance training group (n = 16) exercised at 75% to 85% heart rate reserve for 35 to 45 minutes three times per week; the resistance training group (n = 17) completed one set of eight to 12 repetitions on 10 Nautilus machines three times per week. No significant changes in any variables occurred in a control group (n = 9). Maximal oxygen consumption (VO2max) increased by 20% with endurance training, but did not change with resistance training. Upper- and lower-body strength increased in the resistance training group, but did not change with endurance training. Neither group changed their body weight with training, but the endurance training group elicited a significant reduction in their sum of seven skinfolds and percent body fat. Neither group altered their glucose tolerance with training; however, the endurance training group had lower plasma insulin responses after training compared with the other two groups. Serum lipid and plasma DHEA levels did not change in either the endurance or resistance training groups. Ten days of no exercise following training did not significantly alter body weight or composition, glucose tolerance, plasma insulin responses, or plasma DHEA levels in either the endurance training (n = 10) or resistance training (n = 14) group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Proinsulin and specific insulin concentration in high- and low-risk populations for NIDDM.

Hyperinsulinemia and insulin resistance have been implicated as risk factors for the development of non-insulin-dependent diabetes mellitus (NIDDM). Recent data suggest that proinsulin may comprise a large proportion of immunoreactive insulin in subjects with NIDDM and possibly in those with impaired glucose tolerance (IGT) as well. Increased proinsulin concentrations are thought to be an early indicator of a failing pancreas. We examined proinsulin, insulin (using an assay that does not display appreciable cross-reactivity with proinsulin), and the fasting proinsulin:insulin ratio in 206 nondiabetic Mexican-American (a high-risk population for NIDDM) and 123 nondiabetic non-Hispanic white (a low-risk population for NIDDM) participants in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Mexican-Americans had significantly higher fasting and 2-h proinsulin and insulin levels but similar fasting proinsulin:insulin ratios compared with non-Hispanic whites. After statistical adjustment for age, body mass index, waist-to-hip ratio, and glucose tolerance status, Mexican-Americans continued to have higher fasting and 2-h insulin and fasting and 2-h proinsulin concentrations but similar proinsulin:insulin ratios compared with non-Hispanic whites. The fasting proinsulin:insulin ratio was higher in 85 subjects with NIDDM compared with subjects with IGT or normal glucose tolerance (0.31, 0.09, and 0.07, respectively). Thus, nondiabetic subjects from a high-risk population for NIDDM are hyperinsulinemic (using an assay that does not cross-react with proinsulin) and, further, do not secrete more proinsulin relative to insulin itself than do nondiabetic subjects from a low-risk population.

Diabetes Mellitus, Type 2↗
PubMed1994

Pulsatile insulin secretion from isolated human pancreatic islets.

Insulin secretion from the pancreas is pulsatile. The precise site and function of the pacemaker that regulates insulin periodicity in humans have not been determined. We isolated human pancreatic islets from five cadaver organ donors by collagenase digestion and density gradient purification. After 24 h of culture in CMRL-1066 medium at 37 degrees C, aliquots of 200 islets were perifused (1 ml/min for 120 min) with glucose and other secretagogues in oxygenated Krebs-Ringer bicarbonate solution at 37 degrees C. Samples for insulin measurement were taken every minute, and insulin secretion was analyzed by the Clifton and Steiner cycle detection technique. With 3.3 mM glucose (n = 17), insulin oscillations were demonstrated with a periodicity of 9.8 +/- 0.1 min (means +/- SE), mean amplitude was 16.8 +/- 1.8 pM, and overall mean insulin release was 43.8 +/- 4.2 pM. With 16.7 mM glucose (n = 14), no change of insulin periodicity was observed (10.2 +/- 0.9 min), mean amplitude was 41.4 +/- 10.2 pM (P < 0.01 vs. 3.3 mM glucose), and mean insulin release was 118.2 +/- 19.2 pM (P < 0.01 vs. 3.3 mM glucose). Both at 3.3 and 16.7 mM glucose, the addition of 1.4 mM glucagon (n = 4), 15 mM arginine (n = 4), or 100 micrograms/ml tolbutamide (n = 4) caused no change of insulin periodicity but enhanced mean amplitude and mean insulin release compared with glucose alone. These results show that a pacemaker is located within the islets that regulates pulsatile insulin secretion in humans; the pacemaker is remarkably stable, because its periodicity is not affected by factors altering insulin secretion.

Adult↗
PubMed1991

Cortisol reduces plasticity in the kitten visual cortex.

We investigated the effect of elevated levels of cortisol on plasticity in the visual cortex of the cat. Animals were given daily injections of cortisol i.m. for 20 days starting around 35 days of age. After 10 days they were monocularly deprived, and after an additional 10 days recordings were made from the visual cortex to construct an ocular dominance histogram. The results were compared with those from normal animals of the same age, and with animals monocularly deprived for the same period but not treated with cortisol. Cortisol reduced the ocular dominance shift in a dose-dependent manner, but did not totally abolish it even at the highest doses used. Two other series of animals were recorded, one slightly later in the critical period and one slightly earlier, with care taken to give cortisol before the animals were exposed to light in the morning. In both cases, cortisol reduced the ocular dominance shift but did not abolish it. To interpret these results, we measured levels of plasma cortisol in normal cats of various ages. Average levels were fairly constant between birth and 12 months of age (0.5-1 microgram/dl), and increased slightly after that, but there was a large variation between animals. Thus elevated levels of cortisol can have a substantial effect on plasticity in the visual cortex of the cat, but the decline of the critical period for plasticity between 6 weeks and 3-5 months of age does not seem to be due to a rise in cortisol levels during this time.

2-Amino-5-phosphonovalerate↗
PubMed1991

Islet cell responses to glucose in human transplanted pancreas.

Postsurgery, pancreas transplantation results in alterations of carbohydrate metabolism. Additionally, immunosuppressive therapy impacts on glucose regulation. We evaluated the hormonal and metabolic responses of pancreas allografts, utilizing the hyperglycemic clamp technique coupled with the tritiated glucose methodology, in 11 volunteers who had received simultaneous pancreas-kidney transplantation (P-K) with systemic drainage. Their responses were compared with seven volunteers who had received only a kidney (K) graft and with seven normal control (C) volunteers. Although basal glucose and hepatic glucose output were similar in all three groups, basal insulin, C-peptide, glucagon, and pancreatic polypeptide were highest in the P-K group and lowest in normal subjects. During hyperglycemia, all groups showed a similar characteristic, initial complete suppression of hepatic glucose production, with recovery followed by a later suppression. Peripheral glucose uptake was similar in P-K and C subjects but decreased in K patients. Systemic insulin levels were fourfold higher in the pancreas transplant patients than in healthy subjects. Thus, under basal and hyperglycemic stimulation, 1) hepatic glucose homeostasis is regulated normally, even with pancreatic drainage into the systemic circulation; 2) overall glucose disposal is normal in P-K patients because of marked hyperinsulinemia; and 3) there is loss of tonic inhibition of endocrine pancreatic function secondary to pancreatic denervation.

Adolescent↗