PMC

BG and plasma lipids in NGRs. A) Distribution of HbA1c. B) Nonfed BG. C) Plasma TG. D) Plasma TC. Values are means ± se; n = 43. *P < 0.01; **P < 0.001. E) Correlation between plasma TG and HbA1c in NGRs. y = 0.016x + 4.98; n = 43; P < 10⁻⁸.

Effects of age and gender on metabolic profile in young and aged, male and female NGRs. A) Nonfed BG. B) Plasma HbA1c. C) Plasma TG. D) Plasma cholesterol. Values are means ± se. *P < 0.01; **P < 0.001.

Macroscopic, histological, and ultrastructual images of pancreas tissues obtained from nondiabetic and diabetic NGRs. A) Fluorescent micrograph of pancreas tissues immunostained for insulin (red); nuclei counterstained with DAPI (blue). Scale bar = 100 μm. B) Azur staining. In normal NGRs, islets show well-organized endocrine cells, while in the diabetic animals, islets appear degenerated and smaller in size.

Adipocytokines in NGRs. A) Correlation between plasma adiponectin and BW in NGRs, with equation of regression y = −0.25x + 44.54; n = 43; P < 10⁻³. B) Correlation between plasma adiponectin and HbA1c in NGRs, with equation of regression y = −0.16x + 10.27; n = 43; P < 10⁻⁵. C) Relationship between plasma level of adiponection and non-food-deprived insulin. Animals were divided into 3 groups, based on level of HbA1c (%), nondiabetic (open circle; HbA1c<6.5%), mild (plus symbol; 6.5% <HbA1c<9.0%), and severe (solid circle; HbA1c>9.0%); n = 43. D) Correlation between plasma leptin levels and non-food-deprived insulin in NGRs, with equation of regression y = 0.16x + 0.75; n = 43; P < 10⁻⁷.

Atherosclerotic changes in NGRs. A) Morphology of atherosclerotic lesions. Oil-Red-O stained excised aortas of a normal (nonfed BG=93; male; 19 mo of age) and a diabetic NGR (BG=464; male; 14 mo of age). Lesions frequently found in branching areas of the aortic arch and bifurcations. B) Intima hyperplasia, structural damage in media, and lipid depositions as micrscopic correlates of fatty streaks in diabetic NGR. Toluidine blue-stained 1-μm plastic embedded sections at ×40.

Hypertension in NGRs. Systolic BP was measured using the tail-cuff technique. A) Contribution of body mass to BP in NGRs (≤10 mo of age). Animals with average BW < 120 g (n=31) had significantly lower BP than those with average BW > 120 g (n=14). B) BP in normal and diabetic animals at different ages, as indicated. Diabetic rats (BG>150 mg/dl; n=21) showed significantly higher systemic BP values compared to normal controls (BG<150 mg/dl; n=24). BP values in diabetic animals >10 mo of age (n=29) did not significantly differ from age-matched controls (n=9).

Growth characteristics of NGRs. Male and female NGRs fed normal chow and water were weighed individually at different ages. Animals experienced a growth spurt during the first 20 wk and a smaller weight gain until wk 50. Adult females were on average 10–20 g lighter than males at each time point. Few animals lived beyond wk 52, in most cases due to diabetes-associated complications. Observations n at each time point: males, 3–67; females, 2–70. Data are from 206 males and 200 females.

Macroscopic, histological and ultrastructual images of liver tissues obtained from nondiabetic and diabetic NGRs. A) Gross appearance of representative livers of a normal (left panel; nonfed BG=49 mg/dl; plasma TG=35 mg/dl) and a diabetic NGR (right panel; nonfed BG=270 mg/dl; plasma TG=431 mg/dl). In contrast to the normal appearance of liver in nondiabetic NGRs, liver of diabetic rats was enlarged and showed yellowish markings, typical for steatosis. B) Oil-Red-O staining of frozen sections of livers obtained from nondiabetic (left panel) and diabetic animals (right panel). Mayer’s hematoxylin was used for counterstaining. Scale bar = 100 μm. C) Representative electron microscopic visualization of the cytoplasm of a normal (left panel) and a diabetic NGR (right panel). Arrow, typical lipid microdroplets that are indicative of microvesicular steatosis.

Mild obesity and pronounced hyperlipidemia in NGRs. A) Photo of diabetic (left) and nondiabetic (right) female NGRs. Diabetic NGR (106 g) had high nonfed BG (384 mg/dl) and HbA1c (10.1%), whereas corresponding values for the nonobese age-matched NGR (68 g) were normal (BG, 54 mg/dl; HbA1c, 5.4%). B) Correlation between BW and nonfed BG in NGRs (12–24 wk of age). Weak correlation (r²=0.07) suggests that obesity in NGRs is not a defining factor for MetS development. Male and female, n = 50. C) Representative blood samples from diabetic (left) and normal (right) rats. Milky appearance of plasma of the diabetic animal indicates pronounced dyslipidemia.

Macroscopic, histological and ultrastructual images of kidney tissues obtained from nondiabetic and diabetic NGRs. A) Gross appearance of representative kidneys of a normal (left; 5 mo old; nonfed BG=67 mg/dl; plasma TG=43 mg/dl), a young diabetic (middle; 5 mo old; nonfed BG=251 mg/dl; plasma TG=101 mg/dl), and an aged diabetic NGR (right; 14 mo old; nonfed BG=225 mg/dl; plasma TG=160 mg/dl) NGRs. Compared with kidney of a normal young animal, kidney of the age-matched diabetic animal was enlarged; however, it exhibited a smooth surface, which suggests the existence of early stages of diabetic nephropathy. Kidney of aged diabetic rats was relative to those from young diabetic NGRs smaller in size and showed nodular surface, which suggests the presence of atrophic changes. B) Oil-Red-O staining of frozen sections of kidneys obtained from nondiabetic (left panel) and diabetic animals (right panel). Lipid depositions were prominent in the glomeruli (arrow) and proximal tubule epithelial cells (arrowhead) of young diabetic animals (right panel) but not found in normal controls (left panel). Mayer’s hematoxylin was used for counterstaining. Scale bar = 100 μm. C) Representative electron microscopic visualization of the kidney of a normal (left panel) and a diabetic NGR (right panel). Asterisk indicates amorphous deposits.