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Biomedical subjects

S Efendic

Publications and source records attributed to S Efendic.

At least 109 records · Page 6Linked to original sources
PubMed1994

Insulin responses to glucose in healthy males are associated with adult height but not with birth weight.

OBJECTIVE: To investigate the relations between height, birth weight and insulin secretion. SUBJECTS AND DESIGN: Subjects were selected from a register of all male healthy volunteers who had previously participated in insulin secretion studies. All men in whom a 1-h glucose infusion test had been performed on two or more occasions were selected (n = 88). Subjects were divided into two equally sized groups according to 0-10-min insulin responses. MAIN OUTCOME MEASURES: Insulin responses were measured by standardized glucose infusion tests. Heights and weights were measured on these occasions. Birth weights were obtained from questionnaires and validated from obstetric records. RESULTS: The average height for the 50% of subjects with the lowest insulin response was 3.5 cm less [95% confidence interval (CI): 1.1 to 5.9] than in those with the highest response, P < 0.005. These differences were also significant when expressed relative to heights of national cohorts with the same years of birth [1.7% less in those with lowest response (95% CI: 0.3 to 3.0), P < 0.02 for difference]. However, birth weight (known to 69% of subjects) was not associated with insulin response (3706 +/- 126 g in the 50% with lower insulin response, 3590 +/- 136 g in those with higher insulin response). CONCLUSIONS: An early insulin response to glucose associates with postnatal growth. This suggests that physiological variations in postnatal insulin secretion can influence growth and height in healthy subjects. Furthermore, in the present study group, a low birth weight is not an important determinant of postnatal insulin secretion.

Adult↗
PubMed1994

Insulin-like growth factor-I and insulin have no differential effects on glucose production and utilization under conditions of hyperglycemia.

We have previously shown that in moderately hyperglycemic depancreatized dogs, a glucose-lowering infusion of insulin-like growth factor-I (IGF-I) increased glucose utilization and lactate more, and suppressed glucose production and lipolysis less, than an equipotent glucose-lowering dose of insulin. Similar differences have been observed by others in nondiabetic and diabetic rats. To determine whether the decline in glycemia was important in detecting differential effects of IGF-I and insulin on glucose turnover, IGF-I (0.43 micrograms/kg.min; n = 6) or insulin (0.9 mU/kg.min; n = 9) were infused for 180 min, while hyperglycemia (approximately 180 mg/dl) was maintained. The decline of plasma glucose specific activity was minimized by using the matched step tracer infusion ([6-3H]- and [2-3H]glucose) method. Our results confirmed the approximately 10% potency of IGF-I on glucose metabolism compared to insulin and the lack of effect of IGF-I on insulin clearance. Under conditions of hyperglycemia, the glucose turnover findings were unexpected; there was no difference in the inhibition of glucose production (difference from basal, 2.7 +/- 0.4 mg/kg.min with IGF-I and 2.4 +/- 0.2 with insulin) or the stimulation of glucose utilization (difference from basal, 4.5 +/- 0.8 mg/kg.min with IGF-I and 4.7 +/- 1.3 with insulin). However, lactate increased more (P < 0.01) with IGF-I (from 1230 +/- 163 to a peak of 1903 +/- 349 microM) than insulin (from 1209 +/- 291 to 1535 +/- 340 microM) despite the same increment in glucose utilization. FFA and glycerol declined more with insulin, but the difference was not significant. IGF-I and insulin suppressed plasma amino acids to an equivalent extent. We concluded that 1) the differential effects of IGF-I and insulin on glucose turnover are masked under conditions of hyperglycemia; and 2) because insulin and IGF-I induced the same increment in glucose utilization, but lactate increased more with IGF-I, IGF-I might affect intracellular glucose metabolism differently from insulin. The failure of IGF-I to induce greater glucose utilization than insulin during hyperglycemia, the greater rise in lactate with IGF-I treatment, and the absence of differential effects on proteolysis indicate that IGF-I might have only limited clinical application in the treatment of diabetes.

Animals↗
PubMed1994

Inhibition of nitric oxide synthase by NG-nitro-L-arginine causes a preferential decrease in pancreatic islet blood flow in normal rats and spontaneously diabetic GK rats.

To elucidate the effect of nitric oxide (NO) on the blood flow of the pancreatic islets, the NO synthase inhibitor NG-nitro-L-arginine (N-arg; 25 mg/kg BW) was administered iv to rats 10 min before pancreatic blood flow was measured with a nonradioactive microsphere technique. In male Sprague-Dawley rats, N-arg induced a marked decrease in islet blood flow (16 +/- 4 vs. 44 +/- 8 microliters/min.g pancreas; P < 0.001) and a less pronounced decrease in whole pancreatic blood flow (0.27 +/- 0.04 vs. 0.43 +/- 0.06 ml/min.g; P < 0.05), leading to a markedly decreased fractional islet blood flow (5.5 +/- 0.9% vs. 10.3 +/- 1.3%; P < 0.02). In a second experiment, injection of D-glucose (300 mg/kg BW, iv) in male Sprague-Dawley rats induced a selective increase in islet blood flow (P < 0.05). Such an increase has previously been shown to be mediated by a vagal cholinergic mechanism. Administration of N-arg to these rats resulted in decreased pancreatic (P < 0.05), islet (P < 0.001), and fractional (P < 0.001) islet blood flow, which did not differ from those observed in normoglycemic rats after treatment with N-arg. Furthermore, we studied the mechanism behind the previously described increase in islet blood perfusion, mediated by the vagus nerve, in F1-hybrids of the GK (Goto-Kakizaki) rat, a spontaneous animal model of noninsulin-dependent diabetes mellitus. Administration of N-arg to female GK rats resulted in decreases in islet (P < 0.001), pancreatic (P < 0.01), and fractional islet blood flow (P < 0.001) to the levels observed in female Wistar rats treated in parallel. These data are consistent with the possibility that NO is an important physiological regulator of islet blood flow. Furthermore, the vagally dependent high levels of islet blood flow demonstrated in the GK rat appear to be mediated by a mechanism involving NO.

Amino Acid Oxidoreductases↗
PubMed1994

Pancreatic and islet blood flow in F1-hybrids of the non-insulin-dependent diabetic GK-Wistar rat.

Previous studies have indicated that various conditions under which an increased functional load is posed on the pancreatic islets, e.g. partial pancreatectomy and continuous glucose infusions, may influence the microcirculation of the pancreas. To investigate further the effects of elevated functional demand on the islets, the blood perfusion of the whole pancreas and the pancreatic islets was measured with a microsphere technique in an animal model presenting impaired glucose tolerance and mild hyperglycemia, namely F1-hybrids of the spontaneously non-insulin-dependent diabetic GK-Wistar rat. Normal Wistar rats served as controls. All hybrids had a pathological intraperitoneal glucose tolerance test 1 week before the blood flow measurements, which were performed in 10-12-week-old rats. Both the whole pancreatic and the islet blood flows were increased in the hybrids compared to controls. The fractional islet blood flow, i.e. the fraction of whole pancreatic blood flow diverted through the islets, also was increased in the hybrid rats (12.6 +/- 0.6% vs 9.8 +/- 0.5% in controls, p < 0.01). A bilateral abdominal vagotomy performed 30 min before the blood flow measurement markedly decreased the blood flow values of the islets and the whole pancreas in both groups of rats. After vagotomy, the islet blood flow in the hybrid rats was similar to that of the vagotomized control animals (8.2 +/- 0.8 and 7.5 +/- 1.4%, respectively). It is concluded that the increased pancreatic and islet blood perfusion observed in F1-hybrids of the GK-Wistar rat depends on a mechanism mediated by the vagus nerve.

Animals↗
PubMed1994

Inhibition by rat diazepam-binding inhibitor/acyl-CoA-binding protein of glucose-induced insulin secretion in the rat.

Diazepam-binding inhibitor (DBI) has been localized immunohistochemically in many organs. In porcine and rat pancreas, DBI is present in non-B-cells of the pancreatic islets. Porcine peptide also has been shown to suppress insulin secretion from rat pancreas in vitro. Recently, acyl-CoA-binding protein (ACBP) was isolated from rat liver and shown to be identical structurally to DBI isolated from rat brain. Using this rat DBI/ACBP, we have studied its effects on glucose-stimulated insulin secretion in the rat, both in vivo and in isolated pancreatic islets. Infusion iv of rDBI/ACBP (25 pmol/min) during glucose stimulation induced a moderate and transient reduction of plasma insulin levels. Moreover, rDBI/ACBP suppressed insulin release from batch-incubated isolated islets, stimulated by 16.7 mmol/l glucose, by 24% at 10 nmol/l (p < 0.05) and by 40% at 100 nmol/l (p < 0.01). The peptide (100 nmol/l) also inhibited the insulin response to glucose (16.7 mmol/l) from perifused rat islets by 31% (p < 0.05), mainly by affecting the acute-phase response. Finally, incubation of isolated islets in the presence of rDBI/ACBP antiserum (diluted 1:100 and 1:300) augmented the insulin response to 16.7 mmol/l glucose (p < 0.05 or even less). We conclude that rDBI/ACBP, administered iv or added to the incubation media, suppresses insulin secretion in the rat but that the effect is moderate despite the high concentration used. It is therefore unlikely that the peptide modulates islet hormone release, acting as a classical hormone via the circulation. However, the occurrence of DBI/ACBP in the islets and the enhancing effect by the rDBI/ACBP antibodies on glucose-stimulated insulin release suggest that the peptide is a local modulator of insulin secretion.

Animals↗
PubMed1994

Glucose potentiation of arginine-induced insulin secretion is impaired in subjects with a glucokinase Glu256Lys mutation.

Insulin and glucagon release and insulin sensitivity were investigated in patients with glucokinase deficiency. Five subjects with a missense mutation (Glu256Lys) were studied. They were compared with six healthy subjects with low insulin response but normal glucose tolerance. Insulin and glucagon levels were measured at blood glucose 7.1 +/- 0.1 mmol/l and at 10.9 +/- 0.2 mmol/l with or without arginine (5 g i.v.). Insulin sensitivity was assessed as the ratio between infused glucose and the insulin level (M:I) during hyperglycemic clamps. Glu256Lys subjects were nonobese and had fasting blood glucose 6.7 +/- 0.1 mmol/l (P < 0.001 vs. control group). Insulin release was reduced in response to 11 mmol/l glucose (61% of control group, P < 0.05) as well as to arginine in the presence of 11 mmol/l glucose (54% of control group, P < 0.01). Also, the slope of potentiation, i.e., the enhancement of arginine-induced release as a function of prevailing glucose concentration, was reduced (delta insulin/delta glucose, 47% of control group, P < 0.05). As for glucagon release, the response to arginine was not inhibited normally by glucose, resulting in threefold higher levels at 11 mmol/l glucose versus control subjects. Insulin sensitivity, assessed as M:I, was significantly (P < 0.05) reduced (55% of control group). Glucokinase deficiency thus affects not only insulin responses to glucose per se but also glucose potentiation of responses to non-nutrient secretagogues. Abnormalities in glucagon release and insulin sensitivity coexist with attenuated insulin responses in glucokinase-deficient subjects.

Adult↗
PubMed1994

Impact of diabetic inheritance on glucose tolerance and insulin secretion in spontaneously diabetic GK-Wistar rats.

The impact of genetic factors and maternal diabetes on glucose tolerance and pancreatic beta-cell function was studied in first generation (F1) offspring generated in crosses between the spontaneously diabetic Goto-Kakizaki (GK)-Wistar rat and normoglycemic control Wistar rats (W). The (GK x W) F1 hybrids were offspring of either male GK (mGK) and female Wistar (fW) (mGK x fW) or male Wistar (mW) and female GK (fGK) (mW x fGK) rats. Already at 8 days of age, blood glucose levels were elevated in GK (7.6 +/- 0.5 vs. 4.8 +/- 0.3 mM in W; P < 0.001) and in F1 rats (6.0 +/- 0.3 in mGK x fW and 6.6 +/- 0.4 mM in mW x fGK; both P < 0.01 vs. W). In 2-month-old male rats, glucose (2 g/kg, intraperitoneally) markedly increased blood glucose levels after 60 min in GK rats (18.1 +/- 0.6 vs. 5.5 +/- 0.3 mM in W; P < 0.001) and moderately increased levels in F1 rats (9.9 +/- 0.9 in mGK x fW and 11.6 +/- 1.0 mM in mW x fGK, both P < 0.01 vs. W). Similar patterns were obtained in female rats. Repeated backcrossing of F1 with W rats successively improved glucose tolerance. In perfused pancreases of male rats, the 20-min insulin response to 16.7 mM glucose was -7.44 +/- 5.18 pmol in GK rats, 71.57 +/- 12.25 pmol in W rats, 9.00 +/- 0.89 pmol in mGK x fW rats, and 18.20 +/- 3.97 pmol in mW x fGK rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Feasibility of insulin-glucose infusion in diabetic patients with acute myocardial infarction. A report from the multicenter trial: DIGAMI.

OBJECTIVE: To investigate the effect of insulin-glucose infusion on metabolic control and hypoglycemic episodes and its feasibility and safety in patients with diabetes and myocardial infarction (MI) compared with conventional treatment. RESEARCH DESIGN AND METHODS: Of 327 patients with suspected acute MI 158 were randomized to insulin-glucose infusion for at least 24 h and 169 received conventional therapy. We determined the 24-h blood glucose profile in the infusion group, the degree of metabolic control, hypoglycemic events, and in-hospital complications within the two study groups. RESULTS: Blood glucose fell from 14.6 +/- 2.9 to 9.2 +/- 2.9 mM during the first 24 h in patients receiving insulin-glucose and from 15.8 +/- 4.3 to 12.0 +/- 4.4 mM in control patients (P < 0.01). Serum potassium decreased 0.21 +/- 0.56 mM in the infusion group (P < 0.001) and 0.11 +/- 0.59 mM in the control group (P < 0.05). The difference between the groups was not significant. Twenty-eight of the 158 patients developed an episode of hypoglycemia (blood glucose < 3.0 mM) during the insulin-glucose infusion. There were no significant differences in the number of episodes of ventricular tachyarrhythmias or in ischemic events between patients with and without hypoglycemia. CONCLUSIONS: The protocol outlined in this study gives more rapid and better metabolic control than does conventional treatment. This treatment seems to be a feasible alternative for clinical attempts. Before it can be recommended for general use, the impact on mortality needs to be evaluated.

Aged↗
PubMed1994

Impaired glucose and insulin metabolism in borderline hypertension.

This study investigated glucose and insulin metabolism in borderline hypertension (BHT) defined as repeated diastolic blood pressures (DBP) of 85-94 mmHg. Seventy-five BHT and 75 age-matched normotensive (NT, DBP < or = 80 mmHg) men were recruited from a population screening programme. Plasma lipoproteins were determined and an oral glucose tolerance test was performed (WHO criteria). Fasting insulin was significantly higher in the BHT group (17.2 vs 14.2 mU/ml, p < 0.001), whereas fasting blood glucose levels were similar in the two groups, indicating a reduced insulin sensitivity. The BHT group had significantly lower levels of HDL cholesterol and higher levels of plasma triglycerides, VLDL cholesterol and VLDL triglycerides. When adjusted for BMI these differences disappeared, whereas the basal insulin levels remained significantly elevated (F = 10.7, p < 0.001). These results indicate that an altered glucose and insulin metabolism is present already in the early stages of hypertension. They also suggest that these disturbances are only partly dependent on BMI. This supports the hypothesis that reduced insulin sensitivity could be of importance in the early phases of essential hypertension.

Adult↗
PubMed1994

Glucose infusion instead of preoperative fasting reduces postoperative insulin resistance.

In severe catabolic states, such as burn injury, sepsis and accidental injury, a state of marked insulin resistance is encountered. Insulin resistance is also present after elective surgical treatment, more pronounced with increasingly greater magnitude of operation performed. Results of recent animal experiments have shown that even short periods of food deprivation, reducing carbohydrate reserves, alter responses to stress. This notion resulted in our questioning the rationale of carbohydrate depletion associated with overnight preoperative fasting. Twelve patients undergoing elective open cholecystectomy were randomly given no infusion (control group) or 5 milligrams per kilogram per minute of glucose infusion (glucose group) during preoperative overnight fasting. Insulin sensitivity (M value, milligram per kilogram per minute) was determined using the hyperinsulinemic normoglycemic clamp (plasma insulin level, 65 microunits per milliliter and blood glucose level, 4.5 millimoles per liter) before and the first postoperative day. Preoperative insulin sensitivity was similar in the two groups. Postoperatively, M values decreased by 55 +/- 3 percent (control group) and by 32 +/- 4 percent (glucose group) (p < 0.01). Plasma levels of insulin, c-peptide, glucagon, growth hormone, catecholamines and cortisol in connection with clamps were similar in both groups preoperatively and postoperatively. The present results indicate that active preoperative carbohydrate preservation may improve postoperative metabolism because postoperative occurrence of insulin resistance was reduced with preoperative glucose infusion.

Animals↗
PubMed1993

Abnormal insulin secretion and glucose metabolism in pancreatic islets from the spontaneously diabetic GK rat.

Insulin secretion and islet glucose metabolism were compared in pancreatic islets isolated from GK/Wistar (GK) rats with spontaneous Type 2 (non-insulin-dependent) diabetes mellitus and control Wistar rats. Islet insulin content was 24.5 +/- 3.1 microU/ng islet DNA in GK rats and 28.8 +/- 2.5 microU/ng islet DNA in control rats, with a mean (+/- SEM) islet DNA content of 17.3 +/- 1.7 and 26.5 +/- 3.4 ng (p < 0.05), respectively. Basal insulin secretion at 3.3 mmol/l glucose was 0.19 +/- 0.03 microU.ng islet DNA-1.h-1 in GK rat islets and 0.04 +/- 0.07 in control islets. Glucose (16.7 mmol/l) stimulated insulin release in GK rat islets only two-fold while in control islets five-fold. Glucose utilization at 16.7 mmol/l glucose, as measured by the formation of 3H2O from [5-3H]glucose, was 2.4 times higher in GK rat islets (3.1 +/- 0.7 pmol.ng islet DNA-1.h-1) than in control islets (1.3 +/- 0.1 pmol.ng islet DNA-1.h-1; p < 0.05). In contrast, glucose oxidation, estimated as the production of 14CO2 from [U-14C]glucose, was similar in both types of islets and corresponded to 15 +/- 2 and 30 +/- 3% (p < 0.001) of total glucose phosphorylated in GK and control islets, respectively. Glucose cycling, i.e. the rate of dephosphorylation of the total amount of glucose phosphorylated, (determined as production of labelled glucose from islets incubated with 3H2O) was 16.4 +/- 3.4% in GK rat and 6.4 +/- 1.0% in control islets, respectively (p < 0.01). We conclude that insulin secretion stimulated by glucose is markedly impaired in GK rat islets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

DNA polymorphisms in the human tyrosine hydroxylase/insulin/insulin-like growth factor II chromosomal region in relation to glucose and insulin responses.

The feasibility of disease association studies using polymorphic DNA markers in the tyrosine hydroxylase/insulin/insulin-like growth factor II chromosomal region was indicated by a high degree of linkage disequilibrium found in haplotypes. Haplotypes were resolved in the parents from Scandinavian nuclear families by studying the segregation of eight DNA polymorphisms. Comparison of observed vs expected frequencies of haplotypes, as well as pairwise measures of linkage disequilibrium, indicated a high degree of linkage disequilibrium. Five restriction fragment length polymorphisms linked to the tyrosine hydroxylase/insulin/insulin growth factor II region of chromosome 11 were investigated in relation to Type 2 (non-insulin-dependent) diabetes mellitus, and to glucose and insulin responses to glucose infusion in healthy subjects. No significant differences in genotype frequencies between Type 2 diabetic (n = 53) and healthy subjects (n = 106) were found. A significant association (p < 0.001) was initially found between genotypes defined by a PstI polymorphism located 5' of the tyrosine hydroxylase gene and the early glucose response to a standardized glucose infusion test in healthy subjects. However, a follow-up study of 112 healthy individuals failed to confirm this finding.

Alleles↗
PubMed1993

Deficient activity of FAD-linked glycerophosphate dehydrogenase in islets of GK rats.

In pancreatic islet extracts of rats with hereditary non-insulin-dependent diabetes mellitus (GK rats), the activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase, as measured by either a radioisotopic or colorimetric procedure, only represented 30 to 40% of that found in control rats. This decrease in enzymic activity was not attributable to any sizeable change in either islet DNA content or the relative contribution of insulin-producing beta cells to total islet mass. It contrasted with a normal activity of other mitochondrial dehydrogenases and hexokinase isoenzymes. It coincided, however, with an increased activity of glutamate-pyruvate transaminase, as already observed in adult rats injected with streptozotocin during the neonatal period. The decreased activity of islet FAD-linked glycerophosphate dehydrogenase also contrasted with an increased activity of the same enzyme in the liver of GK, as compared to control rats. In the light of these findings and recent metabolic data collected in intact islets of GK rats, it is proposed that a deficiency of beta-cell FAD-linked glycerophosphate dehydrogenase, the key enzyme of the glycerol phosphate shuttle, may represent a cause of inherited non-insulin-dependent diabetes.

Alanine Transaminase↗
PubMed1993

Decreased beta-cell function in women with previous small for gestational age infants.

Insulin, proinsulin and C-peptide responses to intravenous glucose (glucose infusion test, GIT) and insulin sensitivity were measured in women who previously and for unexplained reasons gave birth to small-for-gestational-age infants (SGA, n = 10) or appropriate-for-gestational-age infants (AGA, n = 11). Insulin sensitivity was evaluated by two different methods, somatostatin-, insulin- and glucose infusion test (SIGIT) and Bergman's minimal model method applied to the frequently samples intravenous glucose tolerance test. The two groups were comparable with regard to age, parity and body mass index. The SGA group exhibited significantly (p < 0.01) lower early (0-10 min) and late (10-60 min) insulin, C-peptide and proinsulin responses during GIT than were seen in the control AGA group. Insulin sensitivity evaluated by the two techniques was increased in the SGA group, significantly so only with the minimal model method. The insulin sensitivity index (Si) according to Bergman was 10.98 +/- 2.10 in the SGA as compared to 4.36 +/- 1.18 x 10(-4)min-1 x uU-1 in the AGA group (antilogged values +/- 95% confidence intervals). Early insulin response (GIT) and Si values were inversely correlated (r = -0.48, p < 0.05).

Adult↗
PubMed1993

Release of catecholamines is increased but does not contribute to the impaired insulin secretion in the perfused pancreata of diabetic rats.

Insulin response to glucose is severely impaired in patients with non-insulin-dependent diabetes mellitus (NIDDM). Also in a rat model of NIDDM, neonatally streptozotocin diabetic rats (STZ), the insulin response to glucose is profoundly suppressed when studied in vivo or in the perfused pancreas. The insulin response was better preserved from isolated islets obtained from patients and STZ rats. Since alpha 2-adrenoceptor stimulation suppresses insulin secretion, catecholamines from intrapancreatic nerve terminals may be involved in the mechanism behind the marked impairment of the glucose-stimulated insulin response in the intact pancreas. We have studied the pancreatic content and release--or overflow--of catecholamines from the isolated, perfused pancreas of STZ rats. The overflow of noradrenaline (NA) in the perfusate was two- to threefold higher in pancreata from STZ than from nondiabetic rats, and perfusion with a high glucose concentration increased the NA overflow in both types of pancreata. Levels of adrenaline (ADR) were always low in perfusates of nondiabetic glands, but increased in five of seven perfusions of STZ glands. The pancreatic contents of NA and ADR were similar in STZ and nondiabetic rats. Pretreatment of rats with reserpine 24 h before perfusions reduced the pancreatic content of NA and ADR by > 90% in both STZ and nondiabetic rats. Reserpine also diminished the overflow of NA in the perfusate from STZ rats by > 90% and from nondiabetic rats by 58-77%. After reserpine, however, glucose-induced insulin release was not enhanced in either STZ or control pancreata. In conclusion, overflow of catecholamines is higher in the pancreas of STZ than of nondiabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Increase in somatostatin to glucagon ratio in islets of alloxan-diabetic dogs: effect of insulin-induced euglycemia.

We have previously shown that acute insulin-induced normalization of glycemia in alloxan-diabetic (A-D) dogs results in marked inhibition of total pancreatic glucagon content, but normalization of somatostatin content. We suggested that this glucagon deficiency might account for A-cell unresponsiveness in diabetes. To examine these changes in detail at the islet level, morphometric and immunologic analyses were carried out on pancreata from four normal (N), four hyperglycemic A-D dogs (HD), and four A-D dogs after acute normalization of glycemia with insulin (ND). The total number of islets per pancreas (3.9 x 10(6) +/- 0.5 x 10(6); determined from the number of islets per square millimetre) was reduced by 60% (p < 0.001) in HD, and this was not affected by acute normalization of glycemia. Insulin content per islet was 1247 +/- 205 pg in N, and this was reduced in both HD and ND to 2 and 5%, respectively (p < 0.001). Similarly, insulin-containing B-cell area was 76 +/- 1% of the total islet area in N, and was unmeasurable in HD and ND. Glucagon content per islet was 89 +/- 6 pg in N, and this was increased by 215% (p < 0.001) in HD, but was normalized in ND. The A-cell area increased concomitantly by 170% from 17 +/- 1 to 46 +/- 2% (p < 0.01) of islet area in HD, and remained elevated in ND.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗