Growth Hormone Secretion, Serum, and Cerebral Spinal Fluid Insulin and Insulin-Like Growth Factor-l Concentrations in Pigs with Streptozotocin-Induced Diabetes Mellitus

Abstract

Diabetes mellitus was induced using streptozotocin in five gilts between 8 and 12 weeks of age. Gilts were maintained with exogenous insulin (INS) except during experimental periods. Four litter-mate gilts served as controls. At 9 months of age, all gilts were ovariectomized, and 30 days after ovariectomy, Experiment (Exp) 1 was conducted. Jugular vein catheters were inserted and blood samples were collected every 10 min for 8 hr. Experiment 2 was conducted when gilts were 11 months of age. Venous blood and cerebrospinal fluid (CSF) samples were collected in the absence (Phase I) or presence (Phase II) of INS therapy. In Experiment 1, plasma glucose concentrations were greater (P < 0.05) in diabetic (465 +/- 17 mg/100 ml) than in control (82 mg +/- 17 mg/100 ml) gilts, whereas serum INS was lower (P < 0.0001) in diabetic gilts (0.3 +/- 0.02 vs 0.9 +/- 0.05 ng/ml) and insulin-like growth factor-I was similar in diabetic and control gilts (32 +/- 3 vs 43 +/- 4 ng/ml, respectively). Mean serum GH concentration was 2-fold greater (P < 0.02) in diabetics (2.8 +/- 0.4 ng/ml) than in control gilts (1.2 +/- 0.2 ng/ml). Diabetic gilts exhibited a greater (P < 0.05) number of GH pulses than control gilts (3.2 +/- 0.4 vs 1.5 +/- 0.3/8 hr, respectively). In addition, GH pulse magnitude was markedly elevated (P < 0.02) in diabetic (5.8 +/- 0.4 ng/ml) compared with control gilts (3.3 +/- 0.6 ng/ml). Mean basal serum GH concentrations were greater (P < 0.07) in diabetic (2.2 +/- 0.5 ng/ml) compared with control gilts (1.0 +/- .1 ng/ml). In Experiment 2, CSF concentrations of insulin-like growth factor-I, INS, GH, and protein were similar for diabetic and control gilts in both phases. Serum GH levels were similar for diabetics and controls in Phase I, but were greater (P < 0.05) in diabetics than in controls in Phase II. CSF glucose levels were greater in diabetic than in control gilts in both the presence (P < 0.003) and absence (P < 0.0002) of INS therapy, whereas plasma glucose was greater (P < 0.003) in diabetic than in control gilts in the absence of INS, but returned to control concentrations in the presence of INS. However, serum GH levels were unchanged after INS therapy in the diabetic gilts. In conclusion, altered GH secretion in the diabetic gilt may, in part, be due to elevated CSF glucose concentrations, which may alter GH-releasing hormone and/or somatostatin secretion from the hypothalamus.

Use of the Gottingen Minipig as a Model of Diabetes, with Special Focus on Type 1 Diabetes Research

“…The minipig has lower fasting plasma levels, compared with humans, for both insulin (Eriksson et al 1989;Faber et al 1978;Fritsche et al 2000;Larsen et al 2001Larsen et al , 2002cMatthews et al 1983;Reaven et al 1976), C-peptide (Faber et al 1978;Larsen et al 2001Larsen et al , 2002c, and glucose (Canavan et al 1997;Ellegaard et al 1995;Eriksson et al 1989;Matthews et al 1983;Fritsche et al 2000;Larsen et al 2001Larsen et al , 2002cReaven et al 1976;Weyer et al 1999), whereas domestic pigs have fasting glucose levels in the same range as in humans (Barb et al 1992;Ramsay and White 2000;Wilson et al 1986). Plasma levels of glucose and insulin increase with age both in minipigs ) and humans (Rosenthal et al 1982), indicating reduced insulin sensitivity and/or beta-cell function (Matthews et al 1985).…”

“…Doses of 100 to 150 mg/kg of STZ have been reported to induce insulin-dependent diabetes in both domestic and minipigs in several studies (Barb et al 1992;Canavan et al 1997;Gabel et al 1985;Grussner et al 1993;Larsen et al 2002c;Wilson et al 1986). One study has reported that 150 mg/kg of STZ failed to induce diabetes in 7-to 8-mo-old Göttingen minipigs, whereas 200 mg/kg resulted in insulin-dependent diabetes ).…”

“…Several stable models of diabetes have been established in domestic pigs and minipigs by using pharmacological induction of beta-cell damage with STZ (Barb et al 1992;Canavan et al 1997;Gabel et al 1985;Gerrity et al 2001;Grussner et al 1993;Marshall 1979;Marshall et al 1980Marshall et al , 1975Mesangeau et al 2000;Pattou et al 1994;Wilson et al 1986). These models have markedly increased fasting plasma glucose and decreased glucose-stimulated insulin secretion, which resemble the functional aspects of type 1 diabetes.…”

“…Models of diabetes based on chemical damage of betacells cover a wide spectrum of hyperglycemia (Barb et al 1992;Boullion et al 2003;Canavan et al 1997;Gabel et al 1985;Grussner et al 1993;Kjems et al 2001;Larsen et al 2002c;Otis et al 2003;Wilson et al 1986), yet all are characterized by reduced insulin secretion and beta-cell mass, two of the major characteristics of human type 1 diabetes (Anon 1998;WHO 1999). However, another very important component in the development of type 1 diabetes-the formation of autoantibodies (Anon 1998;WHO 1999)-has been reported in one minipig to date (Rolandsson et al 2002).…”

Effect of castration on serum concentrations of gonadal hormones, insulin-like growth factor-I and its binding proteins in male pigs

“…It circulates in blood bound to specific binding proteins (IGFBP) of approximately 18 and 43 kDa (Smith, 1984). IGF-I and IGFBPs in serum have been studied in gilts and sows under various experimental conditions including ovariectomy (Barb et al, 1992;Howard and Ford, 1992;Killen et al, 1992;Cox et al, 1994;Klindt et al, 1994). In boars, castration led to a fall in serum GH and IGF-I levels (Arbona et al, 1989;Dubreuil et al, 1989;Louveau et al, 1991).…”